Peripheral AFFERENT NEURONS which are sensitive to injuries or pain, usually caused by extreme thermal exposures, mechanical forces, or other noxious stimuli. Their cell bodies reside in the DORSAL ROOT GANGLIA. Their peripheral terminals (NERVE ENDINGS) innervate target tissues and transduce noxious stimuli via axons to the CENTRAL NERVOUS SYSTEM.
A class of nerve fibers as defined by their nerve sheath arrangement. The AXONS of the unmyelinated nerve fibers are small in diameter and usually several are surrounded by a single MYELIN SHEATH. They conduct low-velocity impulses, and represent the majority of peripheral sensory and autonomic fibers, but are also found in the BRAIN and SPINAL CORD.
Cells specialized to transduce mechanical stimuli and relay that information centrally in the nervous system. Mechanoreceptor cells include the INNER EAR hair cells, which mediate hearing and balance, and the various somatosensory receptors, often with non-neural accessory structures.
Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.
An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.
Act of eliciting a response from a person or organism through physical contact.
An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.
An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.
Cellular receptors which mediate the sense of temperature. Thermoreceptors in vertebrates are mostly located under the skin. In mammals there are separate types of thermoreceptors for cold and for warmth and NOCICEPTORS which detect cold or heat extreme enough to cause pain.
Presence of warmth or heat or a temperature notably higher than an accustomed norm.
The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
A subgroup of TRP cation channels named after vanilloid receptor. They are very sensitive to TEMPERATURE and hot spicy food and CAPSAICIN. They have the TRP domain and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold.
Slender processes of NEURONS, including the AXONS and their glial envelopes (MYELIN SHEATH). Nerve fibers conduct nerve impulses to and from the CENTRAL NERVOUS SYSTEM.
A voltage-gated sodium channel subtype that is expressed in nociceptors, including spinal and trigeminal sensory neurons. It plays a role in the transmission of pain signals induced by cold, heat, and mechanical stimuli.
Specialized afferent neurons capable of transducing sensory stimuli into NERVE IMPULSES to be transmitted to the CENTRAL NERVOUS SYSTEM. Sometimes sensory receptors for external stimuli are called exteroceptors; for internal stimuli are called interoceptors and proprioceptors.
Amount of stimulation required before the sensation of pain is experienced.
The sensation of cold, heat, coolness, and warmth as detected by THERMORECEPTORS.
A class of nerve fibers as defined by their structure, specifically the nerve sheath arrangement. The AXONS of the myelinated nerve fibers are completely encased in a MYELIN SHEATH. They are fibers of relatively large and varied diameters. Their NEURAL CONDUCTION rates are faster than those of the unmyelinated nerve fibers (NERVE FIBERS, UNMYELINATED). Myelinated nerve fibers are present in somatic and autonomic nerves.
The propagation of the NERVE IMPULSE along the nerve away from the site of an excitation stimulus.
Any of several BRASSICA species that are commonly called mustard. Brassica alba is white mustard, B. juncea is brown or Chinese mustard, and B. nigra is black, brown, or red mustard. The plant is grown both for mustard seed from which oil is extracted or used as SPICES, and for its greens used as VEGETABLES or ANIMAL FEED. There is no relationship to MUSTARD COMPOUNDS.
Drugs that act on neuronal sensory receptors resulting in an increase, decrease, or modification of afferent nerve activity. (From Smith and Reynard, Textbook of Pharmacology, 1991, p367)
The three membranes that cover the BRAIN and the SPINAL CORD. They are the dura mater, the arachnoid, and the pia mater.
Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
The semilunar-shaped ganglion containing the cells of origin of most of the sensory fibers of the trigeminal nerve. It is situated within the dural cleft on the cerebral surface of the petrous portion of the temporal bone and gives off the ophthalmic, maxillary, and part of the mandibular nerves.
The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system.
Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.
Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.
Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.
The minimum amount of stimulus energy necessary to elicit a sensory response.
A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN repeats are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.
Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.
A family of proton-gated sodium channels that are primarily expressed in neuronal tissue. They are AMILORIDE-sensitive and are implicated in the signaling of a variety of neurological stimuli, most notably that of pain in response to acidic conditions.
Nerve structures through which impulses are conducted from a peripheral part toward a nerve center.
An increased response to stimulation that is mediated by amplification of signaling in the CENTRAL NERVOUS SYSTEM (CNS).
Sensing of noxious mechanical, thermal or chemical stimuli by NOCICEPTORS. It is the sensory component of visceral and tissue pain (NOCICEPTIVE PAIN).
A voltage-gated sodium channel subtype found in the neurons of the NERVOUS SYSTEM and DORSAL ROOT GANGLIA. It may play a role in the generation of heat and mechanical pain hypersensitivity.
Rapidly decreasing response to a drug or physiologically active agent after administration of a few doses. In immunology, it is the rapid immunization against the effect of toxic doses of an extract or serum by previous injection of small doses. (Dorland, 28th ed)
A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include PAIN; PARESTHESIAS; PARESIS; or HYPESTHESIA.
An absence of warmth or heat or a temperature notably below an accustomed norm.
An alcohol produced from mint oils or prepared synthetically.
A major nerve of the upper extremity. In humans the fibers of the radial nerve originate in the lower cervical and upper thoracic spinal cord (usually C5 to T1), travel via the posterior cord of the brachial plexus, and supply motor innervation to extensor muscles of the arm and cutaneous sensory fibers to extensor regions of the arm and hand.
The functions of the skin in the human and animal body. It includes the pigmentation of the skin.
Inflammation caused by an injurious stimulus of peripheral neurons and resulting in release of neuropeptides which affect vascular permeability and help initiate proinflammatory and immune reactions at the site of injury.
Inflammation of the DENTAL PULP, usually due to bacterial infection in dental caries, tooth fracture, or other conditions causing exposure of the pulp to bacterial invasion. Chemical irritants, thermal factors, hyperemic changes, and other factors may also cause pulpitis.
The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors.
The process by which cells convert mechanical stimuli into a chemical response. It can occur in both cells specialized for sensing mechanical cues such as MECHANORECEPTORS, and in parenchymal cells whose primary function is not mechanosensory.
A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.
A subclass of ADENOSINE RECEPTORS that are generally considered to be coupled to the GS, STIMULATORY G-PROTEIN which causes up regulation of CYCLIC AMP.
Biological actions and events that constitute the functions of the NERVOUS SYSTEM.
A condition where damage to the peripheral nervous system (including the peripheral elements of the autonomic nervous system) is associated with chronic ingestion of alcoholic beverages. The disorder may be caused by a direct effect of alcohol, an associated nutritional deficiency, or a combination of factors. Clinical manifestations include variable degrees of weakness; ATROPHY; PARESTHESIAS; pain; loss of reflexes; sensory loss; diaphoresis; and postural hypotension. (From Arch Neurol 1995;52(1):45-51; Adams et al., Principles of Neurology, 6th ed, p1146)
Neurons in the SPINAL CORD DORSAL HORN whose cell bodies and processes are confined entirely to the CENTRAL NERVOUS SYSTEM. They receive collateral or direct terminations of dorsal root fibers. They send their axons either directly to ANTERIOR HORN CELLS or to the WHITE MATTER ascending and descending longitudinal fibers.
Agents, usually topical, that relieve itching (pruritus).
A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.
Drugs that act principally at one or more sites within the peripheral neuroeffector systems, the autonomic system, and motor nerve-skeletal system. (From Smith and Reynard, Textbook of Pharmacology, 1991, p75)
The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot.
The 5th and largest cranial nerve. The trigeminal nerve is a mixed motor and sensory nerve. The larger sensory part forms the ophthalmic, mandibular, and maxillary nerves which carry afferents sensitive to external or internal stimuli from the skin, muscles, and joints of the face and mouth and from the teeth. Most of these fibers originate from cells of the TRIGEMINAL GANGLION and project to the TRIGEMINAL NUCLEUS of the brain stem. The smaller motor part arises from the brain stem trigeminal motor nucleus and innervates the muscles of mastication.
An antigen solution emulsified in mineral oil. The complete form is made up of killed, dried mycobacteria, usually M. tuberculosis, suspended in the oil phase. It is effective in stimulating cell-mediated immunity (IMMUNITY, CELLULAR) and potentiates the production of certain IMMUNOGLOBULINS in some animals. The incomplete form does not contain mycobacteria.
The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot.
The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
The inferior (caudal) ganglion of the vagus (10th cranial) nerve. The unipolar nodose ganglion cells are sensory cells with central projections to the medulla and peripheral processes traveling in various branches of the vagus nerve.
A protein-tyrosine kinase receptor that is specific for NERVE GROWTH FACTOR; NEUROTROPHIN 3; neurotrophin 4, neurotrophin 5. It plays a crucial role in pain sensation and thermoregulation in humans. Gene mutations that cause loss of receptor function are associated with CONGENITAL INSENSITIVITY TO PAIN WITH ANHIDROSIS, while gene rearrangements that activate the protein-tyrosine kinase function are associated with tumorigenesis.
The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included.
The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium.
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
Either of two extremities of four-footed non-primate land animals. It usually consists of a FEMUR; TIBIA; and FIBULA; tarsals; METATARSALS; and TOES. (From Storer et al., General Zoology, 6th ed, p73)
A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.
The founding member of the glial cell line-derived neurotrophic factor family. It was originally characterized as a NERVE GROWTH FACTOR promoting the survival of MIDBRAIN dopaminergic NEURONS, and it has been studied as a potential treatment for PARKINSON DISEASE.
Use of electric potential or currents to elicit biological responses.
The TEMPERATURE at the outer surface of the body.
Sensation of making physical contact with objects, animate or inanimate. Tactile stimuli are detected by MECHANORECEPTORS in the skin and mucous membranes.
The outermost of the three MENINGES, a fibrous membrane of connective tissue that covers the brain and the spinal cord.
A purinergic P2X neurotransmitter receptor involved in sensory signaling of TASTE PERCEPTION, chemoreception, visceral distension, and NEUROPATHIC PAIN. The receptor comprises three P2X3 subunits. The P2X3 subunits are also associated with P2X2 RECEPTOR subunits in a heterotrimeric receptor variant.
NERVE GROWTH FACTOR is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
The observable response an animal makes to any situation.
An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.
Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.
Compounds capable of relieving pain without the loss of CONSCIOUSNESS.
A richly vascularized and innervated connective tissue of mesodermal origin, contained in the central cavity of a tooth and delimited by the dentin, and having formative, nutritive, sensory, and protective functions. (Jablonski, Dictionary of Dentistry, 1992)
A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes.
Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.
The process by which PAIN is recognized and interpreted by the brain.
Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.
The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.
An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.
A nerve originating in the lumbar spinal cord (usually L2 to L4) and traveling through the lumbar plexus to provide motor innervation to extensors of the thigh and sensory innervation to parts of the thigh, lower leg, and foot, and to the hip and knee joints.
A class of disabling primary headache disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms). (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)
A subgroup of TRP cation channels that contain 3-4 ANKYRIN REPEAT DOMAINS and a conserved C-terminal domain. Members are highly expressed in the CENTRAL NERVOUS SYSTEM. Selectivity for calcium over sodium ranges from 0.5 to 10.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
A heterogenous group of transient or low voltage activated type CALCIUM CHANNELS. They are found in cardiac myocyte membranes, the sinoatrial node, Purkinje cells of the heart and the central nervous system.
A water-soluble extractive mixture of sulfated polysaccharides from RED ALGAE. Chief sources are the Irish moss CHONDRUS CRISPUS (Carrageen), and Gigartina stellata. It is used as a stabilizer, for suspending COCOA in chocolate manufacture, and to clarify BEVERAGES.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
A vesicular glutamate transporter protein that is predominately expressed in the DIENCEPHALON and lower brainstem regions of the CENTRAL NERVOUS SYSTEM.
The process in which specialized SENSORY RECEPTOR CELLS transduce peripheral stimuli (physical or chemical) into NERVE IMPULSES which are then transmitted to the various sensory centers in the CENTRAL NERVOUS SYSTEM.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. (Grant & Hackh's Chemical Dictionary, 5th ed)
A highly reactive aldehyde gas formed by oxidation or incomplete combustion of hydrocarbons. In solution, it has a wide range of uses: in the manufacture of resins and textiles, as a disinfectant, and as a laboratory fixative or preservative. Formaldehyde solution (formalin) is considered a hazardous compound, and its vapor toxic. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p717)
Injuries to the PERIPHERAL NERVES.
Oils derived from plants or plant products.
Disorders of sensory information received from superficial and deep regions of the body. The somatosensory system conveys neural impulses which pertain to proprioception, tactile sensation, thermal sensation, pressure sensation, and pain. PERIPHERAL NERVOUS SYSTEM DISEASES; SPINAL CORD DISEASES; and BRAIN DISEASES may be associated with impaired or abnormal somatic sensation.
A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula.

Adenoviral gene transfer into the normal and injured spinal cord: enhanced transgene stability by combined administration of temperature-sensitive virus and transient immune blockade. (1/1699)

This study characterized gene transfer into both normal and injured adult rat dorsal spinal cord using first (E1-/E3-) or second (E1-/E2A125/E3-, temperature-sensitive; ts) generation of replication-defective adenoviral (Ad) vectors. A novel immunosuppressive regimen aimed at blocking CD4/CD45 lymphocytic receptors was tested for improving transgene persistence. In addition, the effect of gene transfer on nociception was also evaluated. Seven days after treatment, numerous LacZ-positive cells were observed after transfection with either viral vector. By 21 days after transfection, beta-galactosidase staining was reduced and suggestive of ongoing cytopathology in both Ad-treated groups, despite the fact that the immunogenicity of LacZ/Adts appeared less when compared with that elicited by the LacZ/Ad vector. In contrast, immunosuppressed animals showed a significant (P < or = 0.05) increase in the number of LacZ-positive cells not displaying cytopathology. In these animals, a concomitant reduction in numbers of macrophages/microglia and CD4 and CD8 lymphocytes was observed. Only animals that received LacZ/Adts and immunosuppression showed transgene expression after 60 days. Similar results were observed in animals in which the L4-L5 dorsal roots were lesioned before transfection. Gene transfer into the dorsal spinal cord did not affect nociception, independent of the adenovirus vector. These results indicate that immune blockade of the CD4/CD45 lymphocytic receptors enhanced transgene stability in adult animals with normal or injured spinal cords and that persistent transgene expression in the spinal cord does not interfere with normal neural function.  (+info)

Uninjured C-fiber nociceptors develop spontaneous activity and alpha-adrenergic sensitivity following L6 spinal nerve ligation in monkey. (2/1699)

We investigated whether uninjured cutaneous C-fiber nociceptors in primates develop abnormal responses after partial denervation of the skin. Partial denervation was induced by tightly ligating spinal nerve L6 that innervates the dorsum of the foot. Using an in vitro skin-nerve preparation, we recorded from uninjured single afferent nerve fibers in the superficial peroneal nerve. Recordings were made from 32 C-fiber nociceptors 2-3 wk after ligation and from 29 C-fiber nociceptors in control animals. Phenylephrine, a selective alpha1-adrenergic agonist, and UK14304 (UK), a selective alpha2-adrenergic agonist, were applied to the receptive field for 5 min in increasing concentrations from 0.1 to 100 microM. Nociceptors from in vitro control experiments were not significantly different from nociceptors recorded by us previously in in vivo experiments. In comparison to in vitro control animals, the afferents found in lesioned animals had 1) a significantly higher incidence of spontaneous activity, 2) a significantly higher incidence of response to phenylephrine, and 3) a higher incidence of response to UK. In lesioned animals, the peak response to phenylephrine was significantly greater than to UK, and the mechanical threshold of phenylephrine-sensitive afferents was significantly lower than for phenylephrine-insensitive afferents. Staining with protein gene product 9.5 revealed an approximately 55% reduction in the number of unmyelinated terminals in the epidermis of the lesioned limb compared with the contralateral limb. Thus uninjured cutaneous C-fiber nociceptors that innervate skin partially denervated by ligation of a spinal nerve acquire two abnormal properties: spontaneous activity and alpha-adrenergic sensitivity. These abnormalities in nociceptor function may contribute to neuropathic pain.  (+info)

The effects of inflammation and inflammatory mediators on nociceptive behaviour induced by ATP analogues in the rat. (3/1699)

1. We have studied the behavioural effects of intraplantar injections of adenosine 5'-triphosphate (ATP) and related compounds in freely moving rats and investigated whether these nociceptive effects are augmented in the presence of inflammatory mediators. 2. We find that in normal animals ATP and analogues produce dose-dependent nocifensive behaviour (seen as bursts of elevation of the treated hindpaw), and localized thermal hyperalgesia. The rank order of potency was: alpha,beta-methyleneadenosine 5'-triphosphate (alpha,beta-methylene ATP) > 2-methylthioadenosine triphosphate (2-methylthio ATP) > ATP. After neonatal treatment with capsaicin, to destroy small calibre primary sensory neurones, nocifensive behaviour was largely absent. 3. The effects of ATP analogues were assessed in three models of peripheral sensitization: 2 h after dilute intraplantar carrageenan (0.25% w v(-1)); 24 h after irradiation of the hindpaw with ultraviolet (U.V.) B; immediately following prostaglandin E2 (PGE2) treatment. In all models the effect of alpha,beta-methylene ATP was greatly augmented. After carrageenan, significant hindpaw-lifting behaviour activity was induced by injection of only 0.05 nmol of alpha,beta-methylene ATP, some 100 times less than necessary in normal skin. 4. Our data suggest that it is much more likely that endogenous levels of ATP will reach levels capable of exciting nociceptors in inflamed versus normal skin. Our data also suggest the involvement of P2X3 receptor subunits in ATP-induced nociception.  (+info)

The distribution of neurons expressing calcium-permeable AMPA receptors in the superficial laminae of the spinal cord dorsal horn. (4/1699)

The superficial dorsal horn is a major site of termination of nociceptive primary afferents. Fast excitatory synaptic transmission in this region is mediated mainly by release of glutamate onto postsynaptic AMPA and NMDA receptors. NMDA receptors are known to be Ca2+-permeable and to provide synaptically localized Ca2+ signals that mediate short-term and long-term changes in synaptic strength. Less well known is a subpopulation of AMPA receptors that is Ca2+-permeable and has been shown to be synaptically localized on dorsal horn neurons in culture (Gu et al., 1996) and expressed by dorsal horn neurons in situ (Nagy et al., 1994; Engelman et al., 1997). We used kainate-induced cobalt uptake as a functional marker of neurons expressing Ca2+-permeable AMPA receptors and combined this with markers of nociceptive primary afferents in the postnatal rat dorsal horn. We have shown that cobalt-positive neurons are located in lamina I and outer lamina II, a region strongly innervated by nociceptors. These cobalt-positive neurons colocalize with afferents labeled by LD2, and with the most dorsal region of capsaicin-sensitive and IB4- and LA4-positive afferents. In contrast, inner lamina II has a sparser distribution of cobalt-positive neurons. Some lamina I neurons expressing the NK1 receptor, the receptor for substance P, are also cobalt positive. These neurons are likely to be projection neurons in the nociceptive pathway. On the basis of all of these observations, we propose that Ca2+-permeable AMPA receptors are localized to mediate transmission of nociceptive information.  (+info)

Role of protein kinase A in the maintenance of inflammatory pain. (5/1699)

Although the initiation of inflammatory pain (hyperalgesia) has been demonstrated to require the cAMP second messenger signaling cascade, whether this mechanism and/or other mechanisms underlie the continued maintenance of the induced hyperalgesia is unknown. We report that injection of adenylyl cyclase inhibitors before but not after injection of direct-acting hyperalgesic agents (prostaglandin E2 and purine and serotonin receptor agonists) resulted in reduction in hyperalgesia, evaluated by the Randall-Selitto paw-withdrawal test. In contrast, injection of protein kinase A (PKA) inhibitors either before or after these hyperalgesic agents resulted in reduced hyperalgesia, suggesting that hyperalgesia after its activation was maintained by persistent PKA activity but not by adenylyl cyclase activity. To evaluate further the role of PKA activity in the maintenance of hyperalgesia, we injected the catalytic subunit of PKA (PKACS) that resulted in hyperalgesia similar in magnitude to that induced by the direct-acting hyperalgesic agents but much longer in duration (>48 vs 2 hr). Injection of WIPTIDE (a PKA inhibitor) at 24 hr after PKACS reduced hyperalgesia, suggesting that PKACS hyperalgesia is not independently maintained by steps downstream from PKA. In summary, our results indicate that, once established, inflammatory mediator-induced hyperalgesia is no longer maintained by adenylyl cyclase activity but rather is dependent on ongoing PKA activity. An understanding of the mechanism maintaining hyperalgesia may provide important insight into targets for the treatment of persistent pain.  (+info)

Alteration of descending modulation of nociception during the course of monoarthritis in the rat. (6/1699)

Diffuse noxious inhibitory controls (DNIC), which involve supraspinal structures and modulate the transmission of nociceptive signals, were investigated at different stages during the development of adjuvant-induced monoarthritis in the rat. After behavioral evaluation, recordings of trigeminal convergent neurons were performed in anesthetized animals with acute (24-48 hr) or chronic (3-4 weeks) monoarthritis of the ankle. Inhibitions of C-fiber-evoked neuronal responses during and after the application of noxious conditioning stimuli to the ankle were measured to evaluate DNIC. The conditioning stimuli consisted of mechanical (maximal flexion and graded pressures) and graded thermal stimuli and were applied alternately to normal and arthritic ankles. Behaviorally, the two groups of animals exhibited a similar increased sensitivity to mechanical stimuli applied to the arthritic joint (i.e., an increased ankle-bend score and a decreased vocalization threshold to pressure stimuli). However, they showed different electrophysiological profiles. In the animals with acute monoarthritis, the DNIC-induced inhibitions produced by mechanical or thermal stimulation of the arthritic joint were significantly increased at all intensities compared with the normal joint. In contrast, in the chronic stage of monoarthritis, the DNIC-induced inhibitions triggered by thermal or pressure stimuli were similar for both ankles, except with the most intense mechanical stimuli. This discrepancy between the behavioral and electrophysiological findings suggests that inputs activated during chronic monoarthritis may fail to recruit DNIC and may thus be functionally different from those activated in the acute stage of inflammation.  (+info)

Activity-dependent slowing of conduction differentiates functional subtypes of C fibres innervating human skin. (7/1699)

1. The effects of impulse activity on conduction in cutaneous C fibres have been examined in 46 microneurographic recordings from 11 normal subjects and 11 diabetic patients with normal nerve conduction. A tungsten microelectrode was inserted into a cutaneous nerve, usually the superficial peroneal close to the ankle, and intraneural microstimulation was used to identify an area of skin innervated. Three minute trains of 0.25 ms stimuli at 1, 2 and 4 Hz were then delivered to the surface of the skin, separated by intervals of 6 min with stimulation at 0.25 Hz. Slowing and block of conduction were measured from the nerve responses for up to seven C units per stimulation sequence. 2. Three types of C unit were distinguished by their responses to repetitive stimulation: type 1 units slowed progressively during the 3 min trains; slowing of type 2 units reached a plateau within 1 min; while type 3 units hardly slowed at all. Data from normal and diabetic subjects did not differ and were pooled. After 3 min at 2 Hz, the percentage increases in latency were for type 1, 28.3 +/- 9.7 (n = 63 units, mean +/- s.d.); for type 2, 5.2 +/- 1.6 (n = 14); and for type 3, 0.8 +/- 0.5 (n = 5), with no overlap. After 3 min at 4 Hz, 58 % of type 1 units (but no type 2 or 3 units) blocked intermittently. Recovery of latency after stimulation was faster for type 2 than for type 1 units, but conduction velocities of the three types were similar. 3. Type 1 units were identified as nociceptors and 7 type 2 units were identified as 'cold' fibres, activated by non-noxious cold, with no overlap in modality. None of the units tested was activated by weak mechanical stimuli or reflex sympathetic activation. 4. Spike waveforms were averaged for 18 type 1, 10 type 2 and 6 type 3 units. All units had predominantly triphasic action potentials with a major negative peak, but those of type 3 units were on average both smaller and briefer than those of type 1 and type 2 units. 5. It is concluded that repetitive electrical stimulation reliably differentiates nociceptive from cold-specific C fibres innervating human hairy skin, as has previously been shown for the rat. Cold fibres can propagate impulses continuously at much higher rates than nociceptive fibres. The nature of the type 3 units is unclear.  (+info)

Ketamine-induced peripheral analgesia in rats. (8/1699)

AIM: To examine whether ketamine may directly act at peripheral nociceptors to produce analgesia. METHODS: Wistar rats were anesthetized with urethane. As a nociceptive flexion reflex (FR), C responses from the posterior biceps semitendinosus (PBST) muscle was evoked by electrical stimulation (2 ms, 80 V, 2-3 pulses, 0.5 Hz) via a pair of stainless steel needles inserted subcutaneously applied to the two toes of ipsilateral hindpw. RESULTS: Subcutaneous injection of ketamine (36 mmol.L-1, 5 microL) into the ipsilateral hindpaw produced an inhibition of C responses. At 9 min after application of ketamine, injection of naloxone (1%, 5 microL) into the same area annulled ketamine-induced inhibition. CONCLUSION: Ketamine as a dissociate anesthetic acts on peripheral nociceptors to produce analgesia, which is related to activity of peripheral opioid receptors.  (+info)

Fingerprint Dive into the research topics of Spontaneous discharge and increased heat sensitivity of rat C-fiber nociceptors are present in vitro after plantar incision. Together they form a unique fingerprint. ...
The subjective experience of thermal pain follows the detection and encoding of noxious stimuli by primary afferent neurons called nociceptors. However, nociceptor morphology has been hard to access and the mechanisms of signal transduction remain unresolved. In order to understand how heat transducers in nociceptors are activated in vivo, it is important to estimate the temperatures that directly activate the skin-embedded nociceptor membrane. Hence, the nociceptors temperature threshold must be estimated, which in turn will depend on the depth at which transduction happens in the skin. Since the temperature at the receptor cannot be accessed experimentally, such an estimation can currently only be achieved through modeling. However, the current state-of-the-art model to estimate temperature at the receptor suffers from the fact that it cannot account for the natural stochastic variability of neuronal responses. We improve this model using a probabilistic approach which accounts for ...
The effects of axotomy and successful regeneration varied among different groups of cutaneous sensory neurons examined. Among myelinated fibers, nociceptors were found to have decreased thermal and mechanical thresholds, whereas SA1 low-threshold mechanoreceptors exhibited normal thresholds but decreased firing rates to mechanical stimuli. The increase in myelinated nociceptor sensitivity coincided with altered expression of NGF in the reinnervated skin and ASIC3 and TRPV2 in the DRGs. In addition, recent data have described mechanical sensitization of myelinated nociceptors in mice that overexpress NT-3 (McIlwrath et al., 2007). Thus, it should be noted that there was a trend toward increased in NT-3 levels in the skin at 21 d (p = 0.06). Regardless, many myelinated nociceptors do label positively for ASIC3 and/or TRPV2 (McIlwrath et al., 2007; Lawson et al., 2008), and at least some of this increase could be attributable to cells responsive to NGF (Wright and Snider, 1995). The time course of ...
Nociception is the detection of a noxious tissue-damaging stimulus and is sometimes accompanied by a reflex response such as withdrawal. Pain perception, as distinct from nociception, has been demonstrated in birds and mammals but has not been systematically studied in lower vertebrates. We assessed whether a fish possessed cutaneous nociceptors capable of detecting noxious stimuli and whether its behavior was sufficiently adversely affected by the administration of a noxious stimulus. Electrophysiological recordings from trigeminal nerves identified polymodal nociceptors on the head of the trout with physiological properties similar to those described in higher vertebrates. These receptors responded to mechanical pressure, temperatures in the noxious range (more than 40°C) and 1% acetic acid, a noxious substance. In higher vertebrates nociceptive nerves are either A-delta or C fibres with C fibres being the predominating fibre type. However, in the rainbow trout A-delta fibres were most common, and
Tenderness and mechanical allodynia are key symptoms of malignant tumor, inflammation and neuropathy. The proinflammatory cytokine interleukin-6 (IL-6) is causally involved in all three pathologies. IL-6 not only regulates innate immunity and inflammation but also causes nociceptor sensitization and hyperalgesia. In general and in most cell types including immune cells and sensory neurons, IL-6 binds soluble μ receptor subunits which heteromerizes with membrane bound IL-6 signal transducer gp130. In the present study, we used a conditional knock-out strategy to investigate the importance of signal transducer gp130 expressed in C nociceptors for the generation and maintenance of mechanical hypersensitivity. Nociceptors were sensitized to mechanical stimuli by experimental tumor and this nociceptor sensitization was preserved at later stages of the pathology in control mice. However, in mice with a conditional deletion of gp130 in Nav1.8 expressing nociceptors mechanical hypersensitivity by experimental
The Arthrostim® is unique in that it produces a rapid thrust and recoil rate of 12 thrusts / second. This frequency is often referred to as the Low Beta Somato-Motor Rhythm because of its profound effect on the nervous system. This rapidity stimulates specialized nerve pathways that send messages to the brain called proprioceptors and mechanoreceptors which inhibit the nociceptors. Nociceptors are the patient s pain sensing nerve pathways that carry pain messages to the brain.. Also, these nociceptors are not stimulated by the Arthrostim® because of the thrust and recoil. This means that the adjustment can be delivered painlessly to patients of all ages. The Arthrostim® can be used on anyone and is especially useful in our larger than average patients or our pain sensitive patients ...
Nociception is the process whereby specialized somatosensory nerve fibers (nociceptors) detect noxious stimuli and transmit this information to the spinal cord and brain, ultimately evoking a percept of discomfort or pain. Nociceptors are faced with the complex task of detecting disparate environmental and endogenous signals of both a physical and chemical nature, including temperature, pressure, irritants, pruritogens, and inflammatory agents. Consequently, nociceptor activation elicits acute pain as well as injury-evoked pain hypersensitivity, and can contribute to so-called maladaptive processes underlying persistent pain syndromes. Our goal is to understand how nociceptors detect and integrate these signals in response to changing environmental or physiological conditions. We have exploited the vast chemical space of natural product pharmacology to identify and characterize ion channels and sensory neuron subtypes that contribute to distinct nociceptive modalities, with an emphasis on ...
Definition of nociceptors in the dictionary. Meaning of nociceptors. What does nociceptors mean? Information and translations of nociceptors in the most comprehensive dictionary definitions resource on the web.
PRF readers can get free access to a selected Journal of Pain paper each month, thanks to the American Pain Society. Get the free full text of the selection from the December 2017 issue here.. ...
Neuropathic pain is a kind of pathological pain due to a dysfunction of or damage to the nervous system. Peripheral neuropathic pain means pain due to a dysfunction of or damage to 20 Li Li and Xin-Fu Zhou a nerve or group of nerves, primarily peripheral nociceptor afferents (Millan, 1999). Etiologically, it has different types, such as traumatic, metabolic, infectious, toxic, ischaemic, hereditary, compression by tumor and immune-mediated neuropathies (Figure 2). Syndromes of neuropathic pain comprise a complex combination of positive and negative symptoms. 1996). The actions of LTB4 are mediated via its chemotactic action on neutrophils. , 1998a). 4. Effects of NGF on Central Sensitization NGF has been implicated in the spinal processing of nociceptive information. The peripheral action of NGF on the activation and sensitization of primary afferent nociceptors may trigger central changes in the spinal cord. , 1995) to peripheral targets has been shown to increase spinal neuron excitability to ...
inflammation sensitises nociceptors, as we saw above, should our treatment target nociceptiors in IBS? Intuitively, feeling pain should be related to sensing noxious stimuli. However, nociceptor activation does not equate pain perception. For example, spinal anaesthesia blocks acute pain without affecting nociceptor activation. Conversely, visceral pain and the correlated activation of brain structures involved in pain perception can be seen without any afferent input from the organ structure (eg, Song et al). Listening to IBS patients, we typically hear about several different sensations, such as bloating, distension, cramps, urgency or a vague uneasiness, all of which are part of the overall burden of disease, but are not easily accounted for by sensitisation of high threshold nociceptors. Detailed psychophysical experiments in IBS patients generally show lowered thresholds for pain and perceptions related to low intensity stimulation, such as urgency, distension or bloating (eg, Song et al). While
We are interested in investigating the molecular mechanisms that govern the formation and function of pain sensory neurons. In mammals, painful sensory information is detected by a specialized group of sensory neurons called nociceptors. These neurons express a diverse array of ion channels and receptors that underlie the initial reaction to noxious thermal, chemical, and mechanical stimuli. Under pathological conditions - such as inflammation, nerve injuries, or cancer cell invasion - nociceptors can be sensitized, resulting in persistent chronic pain disorders. Few effective medicines are available for neuropathic pain, and over 45% of cancer patients in the United States suffer untreatable pain. A major goal of our research is to understand how distinct classes of nociceptors are specified during development and how nociceptors come to be sensitized during pathological conditions, with the ultimate goal of developing new therapeutic targets for pain treatment.. ...
Nociceptors are receptors in our skin and throughout our bodies that respond to noxious stimuli. For example, when bodily tissue is damaged or subjected to heat or pressure, nociceptors respond and send messages along nerve fibers to our brains, thereby generating the feeling of pain. Teleost fish (fish that are bony such as trout) have nociceptors too, and their nociceptors look just like ours when viewed under a microscope. This does not prove that they feel pain, of course. But they behave i
Abstract: Nociception refers to the detection of noxious mechanical, chemical, or thermal stimuli by specialized neurons called nociceptors. Sensitization of these nociceptor neurons in response to tissue damage or inflammation is a root cause of chronic pain. Protein synthesis is a major regulator of neuronal plasticity, and is thus required for changes in nociceptor sensitivity during the development of chronic pain. The goal of this study was to characterize the components of the eukaryotic initiation complex (eIF4F) that regulate protein translational initiation mechanism in the nociceptors. Drosophila was used as a model organism to study nociceptor function following manipulation of eIF4A, eIF4G1, and eIF4G2 function. Results show that eIF4A is required for normal thermal and mechanical nociception sensitivity as well as sensitization of the nociceptors following tissue damage. eIF4A knockdown larvae showed defects in dendrite morphogenesis, suggesting eIF4A-dependent mRNAs are involved in ...
Inflammatory pain is a result of inflammation or tissue injury. The cells around nociceptors secrete inflammatory mediators; some of them activate nociceptors directly, while other indirectly interfere with the signaling processes inside nociceptors. This results in a reduction of the nociceptor activation threshold, an increase of afferent membrane excitability. Due to intensive firing of primary afferent neurons during the inflammation, numerous changes in the CNS occur, such as central sensitization, hyperalgesia and allodynia. The endogenous opioid system is a major component of the CNS which modulates pain on supraspinal, spinal and peripheral level. Out of the three groups of opioid peptides, enkephalins have a main role in the spinal analgesia. So far, the analgesic effect of botulinum toxin type A is demonstrated in several experimental models of pain. Results of these studies indicate that BT-A acts on a central level, at the spinal cord, where the BT-A is transported through axons from ...
The potential role of the intestinal microbiota in modulating visceral pain has received increasing attention during recent years. This has led to the identification of signaling pathways that have been implicated in communication between gut bacteria and peripheral pain pathways. In addition to the well-characterised impact of the microbiota on the immune system, which in turn affects nociceptor excitability, bacteria can modulate visceral afferent pathways by effects on enterocytes, enteroendocrine cells and the neurons themselves. Proteases produced by bacteria, or by host cells in response to bacteria, can increase or decrease the excitability of nociceptive dorsal root ganglion (DRG) neurons depending on the receptor activated. Short chain fatty acids generated by colonic bacteria are involved in gut-brain communication, and intracolonic short chain fatty acids have pro-nociceptive effects in rodents but may be anti-nociceptive in humans. Gut bacteria modulate the synthesis and release of ...
The following is the transcript for the video above). The third type of pain that I want to talk about is Neuropathic pain.. Neuropathic pain occurs when you have pain because there is some sort of a damage or stress to our nerves (1). Now this can sound awfully like nociceptive pain that we discussed two videos earlier, where certain nerves called nociceptors get simulated and send signals to our brain that can be interpreted as pain.. The difference is, in nociceptive pain, the nociceptors are responding to stresses to SURROUNDING structures, like ligaments, muscles, or bones. Neuropathic pain occurs when the nerves THEMSELVES are compromised, and begin to behave rather irritably.. For example, in shingles, a virus attacks the nerves in our spinal cord, and consequently youll have pain, and even blisters, wherever that nerve goes. Some with diabetes develop peripheral neuropathy where the nerves in the hands and feet become compromised.. And one of the most common neuropathic condition is ...
Chemicals sensitize and activate type IV polymodal nociceptors. Polymodal nociceptors respond to painfully hot and cold temperatures as well as a host of chemical stimuli that activate the nociceptive afferents.
Gate control theory asserts that activation of nerves which do not transmit pain signals, called nonnociceptive fibers, can interfere with signals from pain fibers, thereby inhibiting pain. Afferent pain-receptive nerves, those that bring signals to the brain, comprise at least two kinds of fibers - a fast, relatively thick, myelinated Aδ fiber that carries messages quickly with intense pain, and a small, unmyelinated, slow C fiber that carries the longer-term throbbing and chronic pain. Large-diameter Aβ fibers are nonnociceptive (do not transmit pain stimuli) and inhibit the effects of firing by Aδ and C fibers.. The peripheral nervous system has centers at which pain stimuli can be regulated. Some areas in the dorsal horn of the spinal cord that are involved in receiving pain stimuli from Aδ and C fibers, called laminae, also receive input from Aβ fibers.[7] The nonnociceptive fibers indirectly inhibit the effects of the pain fibers, closing a gate to the transmission of their ...
Nociceptors Tolerance (BB CI 01) is a genetic mutation neuron located on the Neuronal menu. The elements used to fight the effects of an injury are more effective. There are no special requirements for this neuron. The Therapeutic Medication Neuronal Branch The Nociceptors Tolerance (BB CI 01...
Pain occurs when an injury, wound, or disease triggers a response in tissue. Nociceptors are free, peripheral nerve endings that pick up pain stimulus and are present in almost all cell types. These nociceptors transduce stimuli into pain impulses that cause release of chemical mediators. Peripheral nerves conduct pain impulses to the CNS through the spinal cord and up to the brain where they are interpreted as painful. Pain can be activated by an external or internal stimulus such as a dumbbell falling on your foot (external) or bicep tendonitis (internal ...
It is not surprising that the cornea possesses the most dense sensory innervation of the body. It has been estimated that the cornea contains 300-600 times more sensory endings than the skin and 20-40 times more than the tooth pulp. As discussed in this chapter, most of this innervation appears to be nociceptive in nature. This abundance in nociceptive terminals, together with the absence of blood vessels and the structural simplicity of the supporting tissues, makes the cornea a good model for analyzing the morphological and functional properties of peripheral nociceptors.
There are pain receptors - nociceptors - in different parts of the body but not the brain. Scientist Janet Bultitude breaks down what nociceptors are, how they work, and why the brain doesnt have any ...
The long-term objective of this study is to determine how the growth factor artemin (Artn) causes thermal and chemical sensitization of sensory neurons under co...
In the current study, chemical sensitization was localized to the C-fibers in the vicinity of the incision. C-fibers 2 mm or less from the incision showed qualitatively and quantitatively greater responses to pH 6.0 lactic acid compared to sham control or units greater than 2 mm from the incision. In our previous study, we have also shown that heat sensitization of C-fibers are localized to 2 mm or less from the incision.14 These data suggest the possible contribution of the wound environment and the released mediators to the incision-induced peripheral sensitization of nociceptors. One example of these mediators is NGF, which was shown to be increased in skin after incision.26 NGF immunoreactivity was found adjacent to the incision; when examined using Western blot on postoperative day 2, the increase in NGF was in the area immediately surrounding the incision.12 The sensitization of TRPV1 by NGF was shown in vitro .9 In the experiment using isolated sensory neurons and TrkA- and ...
People with osteoarthritis (OA) can have significant pain that interferes with function and quality of life. Women with knee OA have greater pain and greater reductions in function and quality of life than men. In many cases, OA pain is directly related to sensitization and activation of nociceptors in the injured joint and correlates with the degree of joint effusion and synovial thickening. In some patients, however, the pain does not match the degree of injury and continues after removal of the nociceptors with a total joint replacement. Growth of new nociceptors, activation of nociceptors in the subchondral bone exposed after cartilage degradation, and nociceptors innervating synovium sensitized by inflammatory mediators could all augment the peripheral input to the central nervous system and result in pain. Enhanced central excitability and reduced central inhibition could lead to prolonged and enhanced pain that does not directly match the degree of injury. Psychosocial variables can ...
After more than six years of intensive effort, a team of Harvard researchers has successfully converted mouse and human skin cells into pain-sensing neurons
Background Pain is the most debilitating symptom of migraine. The cause of migraine pain likely requires activation of meningeal nociceptors. Mast cell degranulation, with subsequent meningeal nociceptor activation, has ...
Background Pain is the most debilitating symptom of migraine. The cause of migraine pain likely requires activation of meningeal nociceptors. Mast cell degranulation, with subsequent meningeal nociceptor activation, has ...
Sigma-Aldrich offers abstracts and full-text articles by [Rebeca Caires, Enoch Luis, Francisco J Taberner, Gregorio Fernandez-Ballester, Antonio Ferrer-Montiel, Endre A Balazs, Ana Gomis, Carlos Belmonte, Elvira de la Peña].
The transition from acute to chronic pain states might be the most important challenge in research to improve clinical treatment of debilitating pain. We describe a recently identified mechanism of neuronal plasticity in primary afferent nociceptive nerve fibers (nociceptors) by which an acute infla …
Currently, the study of nociception in humans relies mainly on thermal stimulation of heat-sensitive nociceptive afferents. To circumvent some limitations of thermal stimulation, it was proposed that intra-epidermal electrical stimulation (IES) could be used as an alternative method to activate nociceptors selectively. The selectivity of IES relies on the fact that it can generate a very focal electrical current and, thereby, activate nociceptive free nerve endings located in the epidermis without concomitantly activating non-nociceptive mechanoreceptors located more deeply in the dermis. However, an important limitation of IES is that it is selective for nociceptors only when very low current intensities are used. At these intensities, the stimulus generates a very weak percept, and the signal-to-noise ratio of the elicited evoked potentials (EPs) is very low. To circumvent this limitation, it was proposed that the strength of the nociceptive afferent volley could be increased through temporal ...
Fingerprint Dive into the research topics of Loss of Prdm12 during development, but not in mature nociceptors, causes defects in pain sensation. Together they form a unique fingerprint. ...
Despite decades of research, scientists still dont know all the types of neurons that transmit the sensation of mechanical pain. Now, researchers add one more piece to the puzzle, by discovering a new population of specialized mechanosensory nociceptors.
Pain Receptors. The pain receptors in the body are called nociceptors. The specific mechanism by which the nociceptors, on an internal basis, respond to pain is not clearly understood. Researchers believe that it is more complex than just a single response pattern and may include variations in the extracellular matrix, cellular features and even sex hormones that may be signaling the nociceptors. 1 This complicated interplay and variation may account for the different levels of pain various parts of the body respond to and how some people have different pain thresholds than others.. Different nociceptors have different roles in responding to pain. Some respond to heat or cold that is outside of an acceptable range while others respond only to physical damage to the issue or a chemical that is causing a reaction in the cells that is harmful or damaging. The role of pain in this form is to instantly have the brain signal to the body to move, getting the tissue away from any source of damage. ...
Although we all feel pain, were not well-informed on the sensory neurons involved in it. Read on to learn about nociceptors, the pain receptors.
Two important things to take from that definition. First, nociceptors can send information if something is actually being damaged or if they feel there is a threat of damage. The other important part is the brain has to take in the information and make a decision. It can either view the information as credible and create a pain experience so you take some sort of action, or the brain can decide the information from the nociceptors is not relevant and ignore it. This would not result in the experience of pain. So nociceptors can fire and facilitate a pain experience or they can fire and nothing happens. The flip side is your brain can create a pain experience without any information coming in from nociceptors. Now you may be confused, and thats ok. Most people in neuroscience have been confused by this for a very long time and there still isnt a consensus on how this all works.. Now if you think critically about this, it is all really about information. Your brain is taking in a lot of ...
Your sofa may slowly be poisoning you, your wallpaper could be making you cough, and your carpet might be the source of your sniffles. VOCs, or volatile organic compounds, are polluting your indoor air quality, and it is likely that you have never even noticed, or known exactly what is going on in the air space inside your home.
Pain is a multifactorial experience subject to modulation. The basic mechanism of nociception is well established. The pulp is innervated largely by nociceptive fibers, either Aδ (fast conducting; sharp pain) or C fibers (slow conducting; dull, throbbing pain). During inflammation, the C fibers dominate, and pulpal pain is characteristically dull, throbbing, and poorly localized. The periodontal ligament (PDL) has a much greater large-fiber innervation than does the pulp, and many of these fibers are mechanosensitive, which explains why pain from the tooth is more easily localized when inflammation has spread into the supporting tissues. First-order nociceptive fibers connect with second-order neurons in the dorsal horn of grey matter in the spinal cord or in its equivalent in the brainstem, the subnucleus caudalis of the trigeminal system. This is a key relay; it is here that much of the modulation of pain takes place. Through endogenous opioid mechanisms, descending tracts from midbrain areas ...
Inflammatory pain is characterized by an increased response to mechanical or heat stimuli, which are normally only mildly painful (mechanical or thermal hyperalgesia). Inflammatory mediators may elicit pain by activating peripheral nociceptors, by promoting further release of inflammatory mediators and, most significantly, by sensitizing primary afferent neurons to any kind of stimuli. On the other hand, leukocytes may counteract the aforementioned effects of inflammation by releasing opioid peptides in peripheral inflammed tissue. ...
As people age, chronic pain becomes an increasingly common disorder. Scientists have identified chronic pain as a possible risk factor for several pathologies of aging, including cognitive loss. Pain is experienced through the activities of nerve endings called nociceptors, or pain receptors. Chronic nociceptor activity has been shown to induce changes in brain structure and function that may contribute to cognitive loss or dementia.. Molly E. Zimmerman, Ph.D., and colleagues have found that chronic pain can double the risk of dementia in older adults living independently. Using an imaging procedure called structural magnetic resonance imaging (MRI), the researchers also observed that chronic pain was associated with reductions in the volume and metabolic activity of the hippocampus. This area of the brain is closely involved in learning and memory, and it is one of the first brain regions affected by Alzheimers disease.. For their current grant, Dr. Zimmerman and colleagues expect to confirm ...
The pain system involves a set of ascending pathways that convey nociceptive information from peripheral nociceptors via neuronal tracts of the spinal cord to the higher levels of the CNS.
injury when its on a body part that you use all the time. Your brain thinks about your hands at least 10 times more than your arms or your legs. And of course, thinking about your cut means youre focusing on the pain. Plus, cuts on your fingertips are just more painful in general. Since you mainly use your fingers and your hands to feel the world around you, theyre full of nociceptors, pain receptors that respond to things like pressure and temperature. Paper cuts directly damage the nociceptors in your outermost layer of skin, the epidermis, and those nerve bundles send pain signals to your brain. Considering your hands have more nociceptors per square inch than almost any other part of your body, it makes sense that a paper cut on your hand would be much more painful than a paper cut, say, on your arm. Plus, of the different kinds of everyday objects that could cut you, paper is one of the most jagged. A knife will generally leave a clean, residue-free cut, but dull, flexible paper will ...
Nociceptors and immune cells both protect the host from potential threats to homeostasis. There is growing evidence for bidirectional signalling between these two systems, and the underlying mechanisms are beginning to be elucidated. An understanding is emerging of how both the adaptive and innate immune systems can activate and sensitize nociceptors, and, reciprocally, how nociceptors modulate immune cells. In this Review, we discuss how these interactions can be adaptive and useful to the organism but also consider when such signalling might be maladaptive and pathophysiological, contributing to immune-mediated diseases and persistent pain states.
I am interested in molecular determinants regulating responsiveness of neurons to synaptic and sensory stimuli. For such studies my lab utilizes the experimentally tractable model organism, the nematode C. elegans. This model enables concurrent analysis of multiple levels of activity, starting at the molecular level, through the cellular and network levels, and ending with the behavioral level. Specifically, my lab focuses on two research questions: 1) what are the mechanisms regulating the number and properties of neurotransmitter gated ion channels? These studies focus on RIC-3, an evolutionarily conserved chaperone of nicotinic acetylcholine receptors that strongly affects quantity and quality of membrane expressed receptors. 2) What are the signals and signaling pathways regulating responsiveness to noxious stimuli? These studies focus on a pair of C. elegans polymodal sensory neurons, shown to be a well conserved model for polymodal nociceptors. ...
Pain is often addressed in many different subfields, but its molecular neuroscience aspects are incompletely understood. Central and peripheral nervous system pain symptoms affect one out of 5 adults in Western society. This Research Topic is aimed at covering the recent research progress in the molecular neuroscience aspects of the pain field. The neuro-genetics aspects of Migraine and Headache-associated genes, single nucleotide polymorphisms impairing their functioning and the underlying mechanisms of those will be covered by Arn van den Maagdenberg. At the electrophysiology level, Alexander Binshtok and Robert Goldstein will discuss the NaV- independent and -dependent transduction and action potential Initiation zones that form terminal-like structures in the murine peripheral nociceptive nerve trigeminal ganglion, whereas Katharina Zimmerman will focus on the relevant channels, especially TRPA1-carrying C-fibers as contributing to cool and noxious cold sensing in the mouse. At the post
Zhao, J and Lee, M C and Momin, A and Cendan, C M and Shepherd, S T and Baker, M D and Asante, C and Bee, L and Bethry, A and Perkins, J R and Nassar, M A and Abrahamsen, B and Dickenson, A and Cobb, B S and Merkenschlager, M and Wood, J N (2010) Small RNAs Control Sodium Channel Expression, Nociceptor Excitability, and Pain Thresholds. JOURNAL OF NEUROSCIENCE, 30 (32). pp. 10860-10871. ...
Define Nociceptors. Nociceptors synonyms, Nociceptors pronunciation, Nociceptors translation, English dictionary definition of Nociceptors. n. A sensory receptor that responds to pain. American Heritage® Dictionary of the English Language, Fifth Edition. Copyright © 2016 by Houghton Mifflin...
The spared nerve injury (SNI) model of neuropathic pain produces robust and reproducible behavioral mechanical hypersensitivity. Although this rodent model of neuropathic pain has been well established and widely used, peripheral mechanisms underlying this phenotype remain incompletely understood. Here we investigated the role of cutaneous sensory fibers in the maintenance of mechanical hyperalgesia in mice post-SNI. SNI produced robust, long-lasting behavioral mechanical hypersensitivity compared to sham and naïve controls beginning by post-operative day (POD) 1 and continuing through at least POD 180. We performed teased fiber recordings on single cutaneous fibers from the spared sural nerve using ex vivo skin-nerve preparations. Recordings were made between POD 16-42 after SNI or sham surgery. Aδ-mechanoreceptors (AM) and C fibers, many of which are nociceptors, from SNI mice fired significantly more action potentials in response to suprathreshold mechanical stimulation than did fibers from either
TY - JOUR. T1 - Gut nociceptors. T2 - sentinels promoting host defense. AU - Brierley, Stuart M.. PY - 2020/4. Y1 - 2020/4. N2 - Gut-innervating nociceptive neurons detect noxious mechanical and chemical stimuli within our gut, constituting the start of the gut pain pathway. In a recent paper in Cell, Lai et al. report that these nociceptors also play major roles in sensing intestinal bacterial pathogens as well as defending the host by limiting pathogen colonization and invasion.. AB - Gut-innervating nociceptive neurons detect noxious mechanical and chemical stimuli within our gut, constituting the start of the gut pain pathway. In a recent paper in Cell, Lai et al. report that these nociceptors also play major roles in sensing intestinal bacterial pathogens as well as defending the host by limiting pathogen colonization and invasion.. KW - gut pain pathway. KW - intestinal bacterial pathogens. KW - pathogen colonization. UR - ...
TY - JOUR. T1 - Co-expression of µ and d opioid receptors by mouse colonic nociceptors. AU - Guerrero-Alba, Raquel. AU - Valdez-Morales, Eduardo. AU - Jimenez-Vargas, Nestor. AU - Bron, Romke. AU - Poole, Daniel. AU - Reed, David. AU - Castro , Joel. AU - Campaniello, Melissa. AU - Hughes, Patrick. AU - Brierley, Stuart. AU - Bunnett, Nigel. AU - Lomax, Alan. AU - Vanner, Stephen. PY - 2018/3/26. Y1 - 2018/3/26. N2 - Background and Purpose: To better understand opioid signalling in visceral nociceptors, we examined the expression and selective activation of μ and δ opioid receptors by dorsal root ganglia (DRG) neurons innervating the mouse colon. Experimental Approach: DRG neurons projecting to the colon were identified by retrograde tracing. δ receptor-GFP reporter mice, in situ hybridization, single-cell RT-PCR and μ receptor-specific antibodies were used to characterize expression of μ and δ receptors. Voltage-gated Ca 2+ currents and neuronal excitability were recorded in small ...
Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage and serves as a protective mechanism to prevent further damage to the body. The pain experience is different for every individual, as the nature of the injury and our ability to cope with it varies. When tissue damage occurs, pain-sensitive receptors in our body (called nociceptors) are stimulated. As we are recovering from an injury, these receptors remain active and the threshold at which we experience pain is lowered. Once the injury has healed, these receptors become less reactive and the threshold for pain returns to normal levels. Pathological conditions such as Fibromyalgia or Chronic Pain can occur when there is a disruption with how our body processes sensory information, resulting in the individual to experience exaggerated pain responses in the absence of an outside stimulus. Due to serious injuries in the past, the nociceptors can remain highly reactive and the ...
TY - JOUR. T1 - Pain and suffering in invertebrates?. AU - Elwood, R.W.. N1 - Copyright 2012 Elsevier B.V., All rights reserved.. PY - 2011/1/1. Y1 - 2011/1/1. N2 - All animals face hazards that cause tissue damage and most have nociceptive reflex responses that protect them from such damage. However, some taxa have also evolved the capacity for pain experience, presumably to enhance longterm protection through behavior modification based on memory of the unpleasant nature of pain. In this article I review various criteria that might distinguish nociception from pain. Because nociceptors are so taxonomically widespread, simply demonstrating their presence is not sufficient. Furthermore, investigation of the central nervous system provides limited clues about the potential to experience pain. Opioids and other analgesics might indicate a central modulation of responses but often peripheral effects could explain the analgesia; thus reduction of responses by analgesics and opioids does not allow ...
With his research, Powell aims to identify molecular targets to develop novel painkillers that would eliminate the need for opioids in treating chronic inflammatory pain. Current treatment strategies are not suited for long-term pain relief. Pain receptors, known as nociceptors, are sensory neurons that are activated by noxious stimuli. To develop new, non-addictive analgesics, scientists must understand how inflammation produces the change in nociceptor firing that underlies pain perception. The adaptor protein 2 (AP-2) complex is responsible for endocytosis, a basic cellular process where substances and membrane proteins are brought into a cell. Powell is studying the role of the AP-2 complex and endocytosis in the context of inflammatory pain.. Nociceptive dorsal root ganglion (DRG) neurons are central sites for investigative study. During tissue damage, inflammatory mediators initiate signal transduction in DRG neurons - altering channel properties and concomitant pain perception.. Using ...
Miller K.E., J. Balbás, R.L. Benton, T.S. Lam, K.M. Edwards, R.M. Kriebel, and R. Schechter, Glutaminase immunoreactivity and enzyme activity is increased in the rat dorsal root ganglion following inflammation. Special issue: Primary Afferent Nociceptor as a Target for the Relief of Pain. Pain Research and Treatment 2012:414697, 2012; PMID: 22229088. DOI: 10.1155/2012/ ...
Dr. The primary afferent nociceptor. Recently, tezars etal demonstrated that the procedure for screening sidebending t to t. Vaginalis, so additional doses may be allowed to rise to the transverse colon fig. Though a patient for evidence of atlantoaxial instability may develop. The emergency management of pain, if a bat in the form of nonparametric or parametric statistical tests available.
Rainer Haberberger and *Volker Niemeier Institutes for Anatomy and Cell Biology and Psychosomatic Medicine*, Justus-Liebig-University Giessen Neurogenic inflammation of the skin is induced by the activation of nociceptive nerve fibres followed by vasodilation and an increase in vascular permeability. Nociceptors belong to the group of unmyelinated (C-fibre) or myelinated (A-fibre) sensory nerve fibres that innervate different structures in the skin. These fibres originate from dorsal root ganglia (DRG) situated in the intervertebral foramina. Neurochemically distinct populations of sensory DRG neurons project to different regions of the skin. Specific receptors in the endings of those afferent nerve fibres in the skin can be activated by a huge variety of substances including transmitters, proteases, protons and cytokines. Activation of the nerve endings in the skin is followed by the generation of action potentials that are conveyed centrally to the laminae I and II of the spinal cord dorsal ...
Background No satisfactory neurophysiological test for nociceptive afferents is available to date. Laser stimuli present risks of skin damage, whilst electrical stimulation through specially designed electrodes is not selective enough. New method We present a new electrode designed according to critical issues identified in preliminary computer simulations concerning electric field gradient through the skin. To provide selective stimulation the activating electric field must be limited to intraepidermal free nerve endings. To this end, a new interdigitated electrode (IDE) was made of conductive rails arranged in a comb-like micropattern, situated only 150μm apart from each other (150 IDE) and alternately connected to the opposite poles of the stimulator. Results Evoked potentials recorded from the scalp were obtained after stimulation with the 150 IDE and with a similarly designed, but more widely spaced electrode (1000μm, or 1000 IDE). Small amplitude early and medium latency components were recorded
★★★ Nociceptors Acute Pain Chronic Pain Baltimore Pain Relief Center Marketing How Long After A Tooth Extraction Will I Need Pain Relief Best Pain Relief Low…
p,Chronic pain is a major comorbidity of chronic inflammatory diseases. Here, we report that the cytokine IL-1β, which is abundantly produced during multiple sclerosis (MS), arthritis (RA), and osteoarthritis (OA) both in humans and in animal models, drives pain associated with these diseases. We found that the type 1 IL-1 receptor (IL-1R1) is highly expressed in the mouse and human by a subpopulation of TRPV1+ dorsal root ganglion neurons specialized in detecting painful stimuli, termed nociceptors. Strikingly, deletion of the Il1r1 gene specifically in TRPV1+ nociceptors prevented the development of mechanical allodynia without affecting clinical signs and disease progression in mice with experimental autoimmune encephalomyelitis and K/BxN serum transfer-induced RA. Conditional restoration of IL-1R1 expression in nociceptors of IL-1R1-knockout mice induced pain behavior but did not affect joint damage in monosodium iodoacetate-induced OA. Collectively, these data reveal that neuronal IL-1R1 ...
Bradykinin produced at sites of tissue injury and inflammation elicits acute pain and alters the sensitivity of nociceptive neurons to subsequent stimuli. We tested the hypothesis that bradykinin could elicit long-lasting changes in nociceptor function by activating members of the nuclear factor of activated T-cells (NFAT) family of transcription factors. Bradykinin activation of B2 receptors evoked concentration-dependent (EC50 = 6.0 ± 0.3 nM) increases in intracellular Ca2+ concentration ([Ca2+]i) in a proportion of dorsal root ganglion neurons in primary culture. These [Ca2+] increases were sensitive to inhibition of phospholipase C (PLC) and depletion of Ca2+ stores. In neurons expressing a green fluorescent protein (GFP)-NFAT4 fusion protein, a 2-min exposure to bradykinin induced the translocation of GFP-NFAT4 from the cytoplasm to the nucleus. Translocation was partially inhibited by the removal of extracellular Ca2+ and was blocked by inhibition of calcineurin. Furthermore, bradykinin ...
Pain is a complex and subjective experience that involves the transduction of noxious stimuli by nociceptive fibers, but also cognitive and emotional aspects [1]. For instance, human studies indicate that pain is perceived as less intense when individuals are distracted from the pain [2]. Gender and genetic differences also influence the pain perception and a number of animal models have been used to study the influence of these factors on nociception [3]. The Spontaneously Hypertensive Rats (SHR) show abnormal nociceptive reactivity in several nociceptive tests [4-8]. In the hot-plate test, SHR are hypoalgesic when compared to rats of other strains [4, 5, 7, 8], but they show normal properties of nociceptive fibers [9]. We have recently reported that hypoalgesia was no longer observed in SHR rats after habituation to the unheated hot-plate apparatus, suggesting that their hypoalgesic phenotype may involve cognitive processes (e.g. distraction) [8]. This is consistent with the fact that SHR have ...
Increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input.. I dont agree with IASP definition of central sensitization and Ill tell you why.. IASPs revised term expands Woolfs observations to all nociceptive neurons in the CNS, despite:. (i) There is minimal evidence of nociceptive-specific neurons in the CNS. In over 50 years of pain science, less than 300 nociceptive-specific neurons have been identified across different animal studies. You slough off more dead skin cells washing your hands. Note that if a study does not also evaluate a neurons response to non-nociceptive stimuli, it cannot be considered specific to nociception. Thats how science works.. Most recently, Iannettis group showed that the pain matrix-a mythical group of brain regions that was thought to be necessary and sufficient to create the conscious perception of pain-is not specific to pain when the appropriate control tasks are included to account ...
TY - JOUR. T1 - Quantitative assessment of nocifensive behavioral responses and the underlying neuronal circuitry. AU - Carstens, Earl. PY - 1993/12. Y1 - 1993/12. N2 - This paper reviews several recently developed animal models that allow a quantitative assessment of the magnitude of nocifensive behavioral responses across a range of noxious stimulus intensities. Models discussed in detail include: (a) the rodent tail flick reflex, and a modification that allows measurement of tail flick magnitude, (b) rat hindlimb flexion withdrawal reflex elicited by noxious thermal stimulation of the paw, and (c) a learned operant response (nose bar press) evoked by noxious thermal stimulation of the rats tail. These models are discussed in terms of their advantages over previous methods measuring response threshold, their fulfillment of criteria for ideal pain assessment models, and the neuronal circuitry underlying the behavioral response.. AB - This paper reviews several recently developed animal models ...
OBJECTIVE: Osteoarthritis (OA) is a painful degenerative joint disease. To assess joint nociceptor activation indirectly, we used a novel in vitro knee joint preparation and determined the release of calcitonin gene-related peptide (CGRP) and prostaglandin E2 (PGE2) in osteoarthritic mice. METHODS: We studied STR/1N mice, which spontaneously develop OA, along with CD-1 mice as controls and C57/Bl6 mice with unilateral collagenase-induced OA and C57/Bl6 control mice. The release of CGRP and PGE2 from tibial and femoral joint preparations was determined separately in vitro with enzyme immunoassays; we investigated both basal release and release induced by stimulation with capsaicin (CAP, 1 microM) or bradykinin (BK, 10 microM). RESULTS: Basal PGE2 release from femoral and tibial preparations increased by 79% and 97%, respectively, in STR/1N mice between 6 and 18 weeks of age when they developed OA, while age-matched CD-1 mice exhibited only a weak increase (23%). BK-evoked PGE2 release was ...
View more ,TRPV1 is a polymodal nociceptor for diverse physical and chemical stimuli that interact with different parts of the channel protein. Recent cryo-EM studies revealed detailed channel structures, opening the door for mapping structural elements mediating activation by each stimulus. Towards this goal, here we have combined unstructured peptide-insertion screening (UPS) with electrophysiological and fluorescence recordings to explore structural and functional roles of the intracellular regions of TRPV1 in mediating various activation stimuli. We found that most of the tightly packed protein regions did not tolerate structural perturbation by UPS when tested, indicating that structural integrity of the intracellular region is critical. In agreement with previous reports, Ca2+-dependent desensitization is strongly dependent on both intracellular N- and C-terminal domains; insertions of an unstructured peptide between these domains and the transmembrane core domain nearly eliminated ...
I was entranced by an essay in Emergency Physicians Monthly . . . If you want to know what professional craftsmanship looks like, this is it. . -David Brooks, New York Times Op/Ed Editor. ...
Decreased serotonin level during pregnancy alters morphological and functional characteristics of tonic nociceptive system in juvenile offspring of the rat. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
After assessment of SA, each neuron with a dorsal root-evoked somatic spike was tested for sensory modality with natural search stimuli. For full methods of classification of sensory properties, see Fang et al. (2002, 2005b). Briefly, intact neurons were classed as low-threshold mechanoreceptive (LTM) units if they responded to innocuous mechanical stimuli (e.g., light brush, light pressure with a blunt object, and/or vibration). Such light pressure caused a slight deformation of the skin inside the experimenters wrist and resulted in a sensation of touch. C-cooling units were usually spontaneously active at room temperature, and were activated by a cold stimulus (see below) and inhibited by radiant warming but did not respond to mechanical stimuli. Nociceptive units were identified from their responses to noxious stimuli that were applied only to units that failed to respond to any of the above non-noxious stimuli. Noxious stimuli included noxious mechanical (e.g., needle, fine- or ...
The major characteristics of inflammatory and pathological pain are that noxious stimuli are no longer required to generate pain; indeed, pain may arise spontaneously in the absence of any stimulus. Considerable effort devoted to elucidating the mechanisms responsible has revealed that the nociceptive system is capable of undergoing enormous change or plasticity when exposed to inflammatory mediators and growth factors, in response to activity, and after injury (15). The changes occur in nociceptors, whose peripheral terminals become sensitized during inflammation. Furthermore, axons can become sufficiently hyperexcitable to generate spontaneous action potentials, cell bodies undergo dramatic changes in the expression and trafficking of proteins, and synapses in the spinal cord can change their strength or undergo structural reorganization. Similar changes take place in the spinal cord and brain, involving neurons and non-neuronal cells, and these changes are responsible for facilitating the ...
Certain types of neurons are capable of transmitting a pain signal to the brain. As a group, these pain-sensing neurons are called nociceptors, and virtually every surface and organ of the body is wired with them...
Mouraux A, Iannetti GD, Colon E, Nozaradan S, Legrain V, Plaghki L. Belgian Brain Congress 2010, Brussels, Belgium, 17-18 Sept. 2010. slides ...
Theres something else as well: dont want to lose weight? My advice would be to not let it worry you. Or at least not let this weird notion going around these days that what you eat and how much you eat is something that is imbued with moral significance. That self-regarding actions can be thought of otherwise is indicative of an illiberal spirit of the age, I feel. Ill illustrate this with a degree of honesty about myself that Ill no doubt regret later. Slim, toned, fairly fit is where I find myself at my age. Take exercise, all that shit. But as I still also treat my body as a repository for various noxious chemicals, this has slightly less than fuck all to do with healthy living and mostly to do with a narcissistic attempt to delay the comedy of evolution for a few more years so that I can still persuade women younger than myself to sleep with me. Because if theres any truth in the saying that everyone gets the face they deserve by the time theyre fifty, Im gonna look like shit having a ...
Inflammation causes an increased synthesis of COX-2-dependent prostaglan- dins, which sensitize peripheral nociceptor terminals and produce localized pain hypersensitivity. Prostaglandins regulate the sensitivity of so-called poly- modal nociceptors that are ...
Glia dont really care about consequences to a neuromatrixs future, Im sure.. they probably gliafully take full advantage of the opportunity nociceptive input creates for them to run out to yet another yard sale and acquire yet more rusty junk with which to decorate their homes&yards... remember, at a cellular level, even though human body cells are pretty cooperative with each other, at a cellular biological level, its all about whose mitochondria can burn up the most oxygen, and produce the most ATP; all those products nociceptors release at both poles when they become overstimulated acts as fertilizer to surrounding DRG and CNS glia cells, be they ectodermal neural crest-derived or pure mesodermal immune-derived. They are known as trophic factors after all... so, from a glial point of view, its probably like winning the lottery or unexpectedly inheriting a bunch of money from an aunt who just died.) ...
pain signals look to be plastic at the dorsal root ganglion suggesting a peripheral pain mechanism origin. This is a study that looks at pain as bottom-up
Nociception is the neurological process that results in our perception of pain. Those with Migraine have over-reactive, sensitized nociceptors.
Nociceptor hypersensitivity often outlasts the original injury. Untreated, it can even become permanent. Recent pre-clinical peer-reviewed research published by Dr. Ted Price and Dr. Greg Dussor suggests that the ingredients in Teds Pain Cream appear over time to reset the sensitivity threshold of nociceptors to their
Sensory neurons that detect noxious stimuli (nociceptors) typically adopt complex dendritic structures with highly branched arrays directly beneath the skin. Th...
An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve ...
A combination of two drugs can selectively block pain-sensing neurons in rats without impairing movement or other sensations such as touch, according to a new study by National Institutes of Health (NIH)-supported investigators.
Mouse study reveals pain-sensing neurons also help fight skin infections and help prevent its spread. The findings suggest a new type of immunity.
The ouch part of pain begins when something - heat, certain chemicals or a mechanical force - activates special nerve endings called nociceptors.
Nociceptors[edit]. Main article: Nociceptor. Nociceptors respond to potentially damaging stimuli by sending signals to the ... Mechanical nociceptors respond to excess pressure or mechanical deformation.. *Chemical nociceptors respond to a wide variety ... Nociceptors detect different kinds of damaging stimuli or actual damage. Those that only respond when tissues are damaged are ... Thermal nociceptors are activated by noxious heat or cold at various temperatures. ...
Therefore, they satisfy accepted definitions of nociceptors. They also show similarities to vertebrate Aδ nociceptors, ... There have been numerous studies of learning and memory using nociceptors in the sea hare, Aplysia.[18][19][20] Many of these ... Acids are also known to activate nociceptors in the nematode Caenorhabditis elegans and in Hirudo medicinalis, commonly known ... Nociceptors are sensory receptors that respond to potentially damaging stimuli by sending nerve signals to the brain. Although ...
Some nociceptors are unspecialized free nerve endings that have their cell bodies outside the spinal column in the dorsal root ... Nociceptors are categorized according to the axons which travel from the receptors to the spinal cord or brain. After nerve ... Nociceptors have a certain threshold; that is, they require a minimum intensity of stimulation before they trigger a signal. ... Other nociceptors rely on specialised structures in the skin to transduce noxious information such as nociceptive schwann cells ...
In particular, there are no known nociceptors in groups such as plants, fungi, and most insects, except for instance in fruit ... Dozens of different types of nociceptor ion channels have so far been identified, and their exact functions are still being ... Superficial somatic pain is initiated by activation of nociceptors in the skin or other superficial tissue, and is sharp, well- ... At the peripheral end of the nociceptor, noxious stimuli generate currents that, above a given threshold, send signals along ...
Lynn B (1984). "Cutaneous nociceptors". In Winlow W; Holden AV (eds.). The neurobiology of pain: Symposium of the Northern ...
Lynn B (1984). "Cutaneous nociceptors". In Winlow W, Holden AV (ed.). The neurobiology of pain: Symposium of the Northern ...
ISBN 978-1-4377-1604-7. Belmonte, Carlos; Gallar Juana (1996). "6: Corneal Nociceptors". Neurobiology of Nociceptors. Oxford ...
Activation of nociceptors is not necessary to cause the sensation of pain.[11] Damage or injury to nerve fibers that normally ... This alteration of normal activity is explained by molecular and cellular changes of the primary afferent nociceptors in ... Readings of afferent discharges from C nociceptors identified by marking method have also proved helpful in revealing the ...
Learning and memory using nociceptors in the sea hare, Aplysia has been described. Mollusk neurons are able to detect ... Nociceptors: a phylogenetic view. Journal of Comparative Physiology A, 195: 1089-1106 Wasserthal, Lutz T. (1998). Chapter 25: ...
Her publications include: Braithwaite, Victoria (2003). "Do fishes have nociceptors? Evidence for the evolution of a vertebrate ... nociceptors). She showed that fish produce pain-killing opioids in the same way that mammals do. She then investigated whether ...
Nerve impulses from nociceptors may reach the brain, where information about the stimulus (e.g. quality, location, and ... Most insects do not possess nociceptors, one known exception being the fruit fly. In vertebrates, endogenous opioids are ... St John Smith, E.; Lewin, G.R. (2009). "Nociceptors: a phylogenetic view". Journal of Comparative Physiology A. 195 (12): 1089- ... 2003). "Do fishes have nociceptors? Evidence for the evolution of a vertebrate sensory system". Proc Biol Sci. 270 (1520): 1115 ...
Following beak trimming of older or adult hens, the nociceptors in the beak stump show abnormal patterns of neural discharge, ... The beak is a complex, functional organ with an extensive nervous supply including nociceptors that sense pain and noxious ... "Guidance on keeping of Chickens" (PDF). Breward, J., (1984). Cutaneous nociceptors in the chicken beak. Proceedings of the ...
Following beak trimming of older or adult hens, the nociceptors in the beak stump show abnormal patterns of neural discharge, ... Breward, J., (1984). Cutaneous nociceptors in the chicken beak. Proceedings of the Journal of Physiology, London 346: 56 Gentle ...
Pain receptors are known as nociceptors. Two main types of nociceptors exist, A-fiber nociceptors and C-fiber nociceptors. A- ...
Rainbow trout also have corneal nociceptors. Out of 27 receptors investigated in one study, seven were polymodal nociceptors ... Bony fish possess nociceptors that are similar in function to those in mammals. There are two types of nerve fibre relevant to ... ISBN 978-0-7432-4769-6. Rose, J.D. (2003) A Critique of the paper: "Do fish have nociceptors: Evidence for the evolution of a ... Rose concludes there is little evidence that sharks and rays possess the nociceptors required to initiate pain detection in the ...
Brain Brain tissue itself contains no nociceptors; brain tumors cause pain by pressing on blood vessels or the membrane that ... Invasion of soft tissue by a tumor can cause pain by inflammatory or mechanical stimulation of nociceptors, or destruction of ... Tumors can cause pain by crushing or infiltrating tissue, or by releasing chemicals that make nociceptors responsive to stimuli ... and they release chemicals that stimulate nociceptors. As they grow, tumors compress, consume, infiltrate or cut off blood ...
Mechano-sensitive C nociceptors, also known as polymodal C nociceptors are activated by several kinds of stimuli, i.e. ... The mechano-insensitive C nociceptors, also known as silent nociceptors, differ from polymodal afferents in other respects as ... The mechano-insensitive nociceptors may be sensitized particularly by inflammatory mediators to render them mechano-responsive ... Most studies are focused on C nociceptors. The nociceptive C-fibers constitute a very large proportion of somatic afferent ...
Fitzgerald, Maria (1978). The sensitization of cutaneous nociceptors (PhD thesis). University College London. OCLC 926251169. " ...
Fitzgerald studies the developmental physiology and neurobiology of nociceptor circuits in the brain and spinal cord. Her work ... Fitzgerald, Maria (1978). The sensitization of cutaneous nociceptors (PhD thesis). University College London. OCLC 926251169. ...
Once a danger receptor (called 'nociceptor') has been stimulated, the signal travels via the sensory nerve to the dorsal ( ... Interneuron Nociceptor Reflex Solomon; Schmidt (1990). "13". In Carol, Field (ed.). Human Anatomy & physiology (2 ed.). ...
"Bradykinin Induces TRPV1 Exocytotic Recruitment in Peptidergic Nociceptors". Frontiers in Pharmacology. 7: 178. doi:10.3389/ ...
Puri, S. & Faulkes, Z. (2010). "Do decapod crustaceans have nociceptors for extreme pH?". PLOS ONE. 5 (4): e10244. Bibcode: ... which may be specialized nociceptors. The common brown shrimp Crangon crangon and the prawns Palaemon serratus and Palaemon ...
Mechanical nociceptors respond to excess pressure or mechanical deformation, such as a pinch. Chemical nociceptors respond to a ... Nociceptors respond to potentially damaging stimuli by sending signals to the spinal cord and brain. This process, called ... They are found in internal organs as well as on the surface of the body to "detect and protect". Nociceptors detect different ... Nociceptors are responsible for processing pain and temperature changes. The burning pain and irritation experienced after ...
Therefore, not all noxious stimuli are adequate stimuli of nociceptors. The adequate stimuli of nociceptors are termed ... A nociceptive stimulus is defined as "an actually or potentially tissue damaging event transduced and encoded by nociceptors." ...
... people with the condition also have hyper-excitable nociceptors. When people with fibromyalgia are subjected to intense stimuli ...
Thermal nociceptors are activated by noxious heat or cold at various temperatures. Mechanical nociceptors respond to excess ... Chemical nociceptors respond to a wide variety of chemicals, some of which are signs of tissue damage. They are involved in the ... Nociceptors detect different kinds of damaging stimuli or actual damage. Those that only respond when tissues are damaged are ... Nociceptors respond to potentially damaging stimuli by sending signals to the spinal cord and brain. This process, called ...
Snider, W. D.; McMahon, S. B. (Apr 1998). "Tackling pain at the source: new ideas about nociceptors". Neuron. 20 (4): 629-32. ... as the neck of the posterior column and receives information from mechanoreceptors and danger information from nociceptors. It ...
Formaldehyde Nociceptor Withdrawal reflex Carter, Matt; Shieh, Jennifer C. (2010). "Nociception". Guide to Research Techniques ... reflecting direct activation of nociceptors and the late or tonic phase (15 to 20 minutes after the injection) reflecting ... caused by stimulation of nociceptors. These assays measure the existence of pain through behaviors such as withdrawal, licking ...
Therefore, nociceptors are easily sensitised by agents such as bradykinin and nerve growth factor, which are released at the ... Nociceptors are different from other sensory neurons in that they have a low activating threshold and consequently increase ... Nav1.8 and Nav1.9 are both expressed in nociceptors (damage-sensing neurons). Nav1.7, Nav1.8 and Nav1.9 are found in the DRG ... However, Nav1.8 is cold-resistant and is able to generate action potentials in the cold to carry information from nociceptors ...
Nociceptor Last post by Slava « Sat Aug 14, 2021 9:01 am ...
  • All neurons derived from the neural crest, including embryonic nociceptors, express the TrkA, which is a receptor to nerve-growth factor (NGF). (
  • Specialized peripheral sensory neurons known as nociceptors alert us to potentially damaging stimuli at the skin by detecting extremes in temperature and pressure and injury-related chemicals, and transducing these stimuli into long-ranging electrical signals that are relayed to higher brain centers. (
  • These high threshold physical and noxious chemical stimuli are detected by specialized peripheral sensory neurons (nociceptors). (
  • Gut-Innervating Nociceptor Neurons Regulate Peyer's Patch Microfold Cells and SFB Levels to Mediate Salmonella Host Defense. (
  • Profiling of how nociceptor neurons detect danger - new and old foes. (
  • Nociceptors are sensory neurons that are found in external tissues such as skin , cornea and mucosa as well as in internal organs, such as the muscle , joint , bladder and gut . (
  • Extracellular microRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1. (
  • Here we report an unconventional role of extracellular miRNAs for rapid excitation of nociceptor neurons via toll-like receptor-7 (TLR7) and its coupling to TRPA1 ion channel. (
  • Thus, secreted extracellular miRNAs may serve as novel pain mediators via activating TLR7/TRPA1 in nociceptor neurons. (
  • Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts. (
  • We identified five transcription factors that reprogram mouse and human fibroblasts into noxious stimulus-detecting (nociceptor) neurons. (
  • These recapitulated the expression of quintessential nociceptor-specific functional receptors and channels found in adult mouse nociceptor neurons, as well as native subtype diversity. (
  • Moreover, the derived nociceptor neurons exhibited TrpV1 sensitization to the inflammatory mediator prostaglandin E2 and the chemotherapeutic drug oxaliplatin, modeling the inherent mechanisms underlying inflammatory pain hypersensitivity and painful chemotherapy-induced neuropathy. (
  • Recent studies have demonstrated an important role for T-type Ca 2+ channels (T-channels) in controlling the excitability of peripheral pain-sensing neurons (nociceptors). (
  • After injury, peripheral pain-sensing neurons (nociceptors) can become hyperexcitable, or "sensitized. (
  • However, a causal relationship has been difficult to establish and it is not clear whether vitamin D metabolites directly influence nociceptors (`pain-sensing' neurons). (
  • This study was undertaken to explore whether IL-17A acts on neurons, whether it sensitizes joint nociceptors, and whether neutralization of IL-17 is antinociceptive. (
  • Neurotrophin NGF controls survival of nociceptors, which are pain and temperature sensing neurons expressing NGF receptor TrkA during development and projecting to dorsal spinal cord centrally and to skin in the periphery [1] , [2] . (
  • However, when survival of nociceptors from mice lacking NGF or TrkA was rescued by concomitant deletion of a pro-apoptotic protein Bax, these neurons failed to express such nociceptor-specific protein markers as CGRP and substance P, suggesting that NGF/TrkA signaling also controls gene expression in nociceptors [4] . (
  • In addition to controlling survival and maturation of cutaneous nociceptors, NGF is critical for axonal extension and peripheral target innervation by these neurons. (
  • It's a really interesting study because the field has long assumed that nociceptors make free nerve endings in the skin and don't innervate specialized structures, but these fast-conducting pain neurons actually do by wrapping around guard hair follicles in the mouse's skin," says Cheryl Stucky, Medical College of Wisconsin, Milwaukee, US, who was not involved in the study. (
  • We tested the hypotheses that PGE 2 -G is increased in DRGs of HbSS-BERK mice and sensitizes nociceptors (sensory neurons that respond to noxious stimuli), and that blocking its synthesis would decrease hyperalgesia in HbSS-BERK mice. (
  • Incontrast, ablating Nav1.8 + sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large-pore ion channels to specifically block nociceptors, substantially reduced ovalbumin- or house-dust-mite-induced airway inflammation and bronchial hyperresponsiveness. (
  • Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma. (
  • Pain receptors, also called nociceptors, are a group of sensory neurons with specialized nerve endings widely distributed in the skin, deep tissues (including the muscles and joints), and most of visceral organs. (
  • At the anatomical level, fish have neurons known as nociceptors, which detect potential harm, such as high temperatures, intense pressure, and caustic chemicals. (
  • The resulting neurons express canonical markers and functional properties of human nociceptors, including tetrodotoxin (TTX)-resistant, SCN10A-dependent sodium currents and response to nociceptive stimuli such as ATP and capsaicin. (
  • In mammals, nociceptors are sensory neurons that are found in any area of the body that can sense noxious stimuli either externally or internally. (
  • Background and Purpose: To better understand opioid signalling in visceral nociceptors, we examined the expression and selective activation of μ and δ opioid receptors by dorsal root ganglia (DRG) neurons innervating the mouse colon. (
  • These neurons represent the majority of epidermal afferents in hairy skin, and are predominantly C-fiber polymodal nociceptors (CPMs), responding to mechanical stimulation, heat and in some cases cold. (
  • Cell size of primary sensory neurons and distribution patterns of neurons that are immunopositive (ip) for VRL-1, a newly cloned capsaicin-receptor homologue, were examined in trigeminal ganglia (TGs) of knockout mice for trkA, trkB or trkC to determine the developmental dependency of myelinated nociceptors on expression of the genes. (
  • Small unmyelinated sensory neurons classified as nociceptors are divided into two subpopulations based on phenotypic differences, including expression of neurotrophic factor receptors. (
  • Pain is experienced when nociceptors (pain receptors) in the tissues are activated by chemical mediators released from damaged or stressed cells. (
  • The specific receptors for these intense stimuli were called nociceptors. (
  • They are classified as either peptidergic or nonpeptidergic nociceptors, each of which express a distinct repertoire of ion channels and receptors. (
  • Nociceptors often referred to as your 'pain receptors,' are free nerve endings located all over the body, including the skin, muscles, joints, bones, and internal organs. (
  • It was shown here, via immunohistochemistry and western blot, that rat putative nociceptors contain vitamin D receptors (VDRs) and metabolic enzymes, whose expression is regulated by ovarian hormones. (
  • Interleukin-17 sensitizes joint nociceptors to mechanical stimuli and contributes to arthritic pain through neuronal interleukin-17 receptors in rodents. (
  • This study provides the first in vivo evidence that intracellular parts of different Trk receptors are interchangeable to promote survival and maturation of nociceptors and shows that these developmental processes can be uncoupled from peripheral target innervation. (
  • Our results indicate that anandamide excited cutaneous C nociceptors and produced nocifensive behaviors via activation of TRPV1 receptors. (
  • Nociceptors include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli. (
  • Nociceptors are receptors, which respond to noxious stimuli (stimuli that would cause tissue injury if they were to persist) and their activation results in the sensation of pain . (
  • Cutaneous receptors include cutaneous mechanoreceptors, nociceptors (pain) and thermoreceptors (temperature). (
  • Read on to learn about nociceptors, the pain receptors. (
  • In this article, we'll be talking about nociceptors, the pain receptors. (
  • We conclude that the contribution of CB1-type receptors expressed on the peripheral terminals of nociceptors to cannabinoid-induced analgesia is paramount, which should enable the development of peripherally acting CB1 analgesic agonists without any central side effects. (
  • Conclusions and Implications: A significant number of small diameter colonic nociceptors co-express μ and δ receptors and are inhibited by agonists and endogenous opioids in inflamed tissues. (
  • DOMS may also have a lot to do with specialized pain receptors called nociceptors that lie in the spaces between muscle cells. (
  • Nociceptors are categorized according to the axons which travel from the receptors to the spinal cord or brain. (
  • External nociceptors are found in tissue such as the skin (cutaneous nociceptors), the corneas, and the mucosa. (
  • Heat sensitization of cutaneous nociceptors is observed after burns, and sensitization of articular afferents to limb movements occurs after knee joint inflammation. (
  • Others, using different models of peripheral inflammation, have only rarely found mechanical sensitization of cutaneous nociceptors. (
  • In the current experiments, the mechanical and heat responses of cutaneous nociceptors supplying the glabrous skin of the rat hindpaw were studied 16-24 h after induction of acute inflammation with complete Freund's adjuvant. (
  • Andrew, D & Greenspan, JD 1999, ' Mechanical and heat sensitization of cutaneous nociceptors after peripheral inflammation in the rat ', Journal of neurophysiology , vol. 82, no. 5, pp. 2649-2656. (
  • External examples are in tissues such as skin (cutaneous nociceptors), cornea and mucosa. (
  • All nociceptors are free nerve endings. (
  • Different nociceptors/free nerve endings, and the fibers carrying pain sensation from the nociceptors to the spinal cord. (
  • Some nociceptors are unspecialized free nerve endings that have their cell bodies outside the spinal column in the dorsal root ganglia. (
  • Following sensory neurogenesis, differentiation occurs, and two types of nociceptors are formed. (
  • There are several types of nociceptors and they are classified according to the stimulus modalities to which they respond: i.e. thermal, mechanical or chemical. (
  • What are the three types of nociceptors? (
  • In ovariectomized rats a vitamin D deficient diet induces balance deficits and deep tissue mechanical hyperalgesia, concurrent with muscle hyperinnervation by presumed nociceptors. (
  • Systemic administration of R-flurbiprofen preferentially reduced production of PGE 2 -G over that of PGE 2 in DRGs, decreased mechanical and thermal hyperalgesia, and decreased sensitization of nociceptors in HbSS-BERK mice. (
  • The same dose of R-flurbiprofen had no behavioral effect in HbAA-BERK mice (the transgenic control), but local injection of PGE 2 -G into the hind paw of HbAA-BERK mice produced sensitization of nociceptors and hyperalgesia. (
  • Systemic administration of R-flurbiprofen preferentially reduced production of PGE2-G over that of PGE2 in DRGs, decreased mechanical and thermal hyperalgesia, and decreased sensitization of nociceptors in HbSS-BERK mice. (
  • It was concluded that the mechanical hyperalgesia caused by peripheral inflammation could be explained by nociceptor sensitization. (
  • Injury to tissues can result in }sensitization} of nociceptors, resulting in enhanced response to noxious and normally non-noxious stimuli (i.e., hyperalgesia and allodynia, respectively). (
  • We hypothesize that opiate-induced hyperalgesia and allodynia may result from sensitization of nociceptors. (
  • Polymodal nociceptors respond to mechanical, thermal, and chemical stimuli. (
  • Polymodal nociceptors respond to damaging stimuli of a chemical, thermal, or mechanical nature (Kandel et al, 2000). (
  • Serosal units displayed sensitivity to key algesic mediators, bradykinin (6/14 units tested) and ATP (4/10), consistent with a role as polymodal nociceptors, while muscular afferents are largely insensitive to bradykinin (0/11) and ATP (1/10). (
  • Importantly, these include a population of polymodal nociceptors that preferentially respond to algogenic stimuli and are located in the serosa. (
  • In short, there are three major classes of nociceptors in the skin: Aδ mechanosensitive nociceptors, Aδ mechanothermal nociceptors, and polymodal nociceptors, the latter being specifically associated with C fibers. (
  • Polymodal nociceptors are a challenge for scientists because they respond to every type of stimuli we mentioned above. (
  • 3. Amongst the nociceptor population, C-mechanoheat fibres (C-MH or polymodal nociceptors) were markedly more responsive to P2X agonists than mechanonociceptors (C-M nociceptors) with A{delta}- or C-fibre axons. (
  • The increased neural response under inflammatory conditions was largely observed in C-mechanoheat or polymodal nociceptors. (
  • Chemical nociceptors respond to chemicals released from tissue damage (for example, prostaglandins and substance P) or from external chemicals (for example, topical capsaicin). (
  • Capsaicin weakly activates conventional C-fiber nociceptors , but produces a vigorous response in a subtype of C-fiber nociceptors that are insensitive to mechanical stimuli. (
  • Moreover, subcutaneous HA injection in mice reduces heat and capsaicin nocifensive responses, whereas the intra-articular injection of HA in rats decreases capsaicin joint nociceptor fibres discharge. (
  • To elucidate if these fibers also contribute to allergic airway inflammation, we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. (
  • We evaluated whether activation of the NPY Y1 receptor could modulate the activity of capsaicin-sensitive nociceptors in trigeminal ganglia and dental pulp. (
  • We tested this hypothesis by measuring capsaicin-stimulated calcitonin gene-related peptide release (CGRP) as a measure of nociceptor activity. (
  • These results demonstrate that activation of the Y1 receptor results in the inhibition of the activity of capsaicin-sensitive nociceptors in the trigeminal ganglia and dental pulp. (
  • This phenomenon, "hyperalgesic priming," depends on the epsilon isoform of protein kinase C (PKCepsilon) and a switch in intracellular signaling pathways that mediate cytokine-induced nociceptor hyperexcitability. (
  • Hyperexcitability in mechanoinsensitive C-nociceptors was significantly higher in patients with polyneuropathy and pain compared to patients with polyneuropathy without pain, while the difference was much less prominent in mechanosensitive (polymodal) C-nociceptors. (
  • We therefore conclude that rather than being a generic sign of neuropathy, multiple spiking is linked to axonal hyperexcitability and spontaneous activity of nociceptors. (
  • PDN is characterized by neuropathic pain and small-fiber degeneration, accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability and loss of their axons within the skin. (
  • The molecular mechanisms underlying DRG nociceptor hyperexcitability and small-fiber degeneration in PDN are unknown. (
  • Hence, we propose that targeting CXCR4-mediated DRG nociceptor hyperexcitability is a promising therapeutic approach for disease-modifying treatments for this currently intractable and widespread affliction. (
  • Transient receptor potential vanilloid I (TRPV1) sensitization in peripheral nociceptors is a prominent phenomenon that occurs in inflammatory pain conditions. (
  • Pro-algesic agents can potentiate TRPV1 activity in nociceptors through both stimulation of its channel gating and mobilization of channels to the neuronal surface in a context dependent manner. (
  • A recent study reported that ATP-induced TRPV1 sensitization in peptidergic nociceptors involves the exocytotic release of channels trafficked by large dense core vesicles (LDCVs) that cargo alpha-calcitonin gene related peptide alpha (αCGRP). (
  • We hypothesized that, similar to ATP, bradykinin may also use different mechanisms to sensitize TRPV1 channels in peptidergic and non-peptidergic nociceptors. (
  • We found that bradykinin notably enhances the excitability of peptidergic nociceptors, and sensitizes TRPV1, primarily through the bradykinin receptor 2 pathway. (
  • Notably, bradykinin sensitization of TRPV1 in peptidergic nociceptors was significantly blocked by inhibiting Ca 2+ -dependent neuronal exocytosis. (
  • In addition, silencing αCGRP gene expression, but not substance P, drastically reduced bradykinin-induced TRPV1 sensitization in peptidergic nociceptors. (
  • Taken together, these findings indicate that bradykinin-induced sensitization of TRPV1 in peptidergic nociceptors is partially mediated by the exocytotic mobilization of new channels trafficked by αCGRP-loaded LDCVs to the neuronal membrane. (
  • Physiologically, TRPV1 acts as a major integrator of painful stimuli in nociceptors. (
  • Hyaluronan modulates TRPV1 channel opening, reducing peripheral nociceptor activity and pain. (
  • Collectively, these results indicate that extracellular HA reduces the excitability of the ubiquitous TRPV1 channel, thereby lowering impulse activity in the peripheral nociceptor endings underlying pain. (
  • Note: Neuromics' TRPV1 Antibody was used as a marker for mature nociceptors. (
  • A nociceptor ("pain receptor") is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals to the spinal cord and the brain. (
  • A nociceptor is a sensory receptor that sends signals that cause the perception of pain in response to potentially damaging stimulus. (
  • Thus, serosal afferents (putative nociceptors) were used to investigate the effect of tegaserod, and transient receptor potential channel, vanilloid 4 (TRPV 4 ) modulation on mechanical responses. (
  • Human serosal visceral nociceptor mechanosensitivity is attenuated by treatment with the transient receptor potential channel, vanilloid 4 (TRPV 4 ) antagonist (HC067047), highlighting the therapeutic potential of TRPV 4 blockade for the treatment of visceral pain. (
  • Finally, it has been shown that expression of NT3 receptor TrkC from TrkA locus engaged a subset of former TrkA nociceptors to become TrkC-expressing proprioceptors [9] . (
  • Nociceptors with peripheral and central projections express temperature sensitive transient receptor potential (TRP) ion channels, also called thermoTRPs. (
  • Gibbs, JL & Harqreaves, KM 2008, ' Neuropeptide Y Y1 receptor effects on pulpal nociceptors ', Journal of dental research , vol. 87, no. 10, pp. 948-952. (
  • Approximately half of unmyelinated nociceptors express the NGF receptor TrkA, and half express the GDNF family ligand (GFL) receptor Ret. (
  • Pain is transmitted to the central nervous system (CNS) in two separate ways via myelinated A delta fibers and unmyelinated C fibers, following the induction of nociceptors (3). (
  • We describe a recently identified mechanism of neuronal plasticity in primary afferent nociceptive nerve fibers (nociceptors) by which an acute inflammatory insult or environmental stressor can trigger long-lasting hypersensitivity of nociceptors to inflammatory cytokines. (
  • When an injury occurs (such accidentally cutting your finger with a knife), the stimulated nociceptors activate the A fibers, causing a person to experience sharp, prickling pain. (
  • Action potentials generated in nociceptors and injured nerve fibers release excitatory neurotransmitters at their synaptic terminals such as L-glutamate and substance P and trigger cellular events in the central nervous system that extend over different time frames. (
  • We investigated the effect of isoflurane on 2 main types of thermal nociceptors: A-δ and C-fibers. (
  • Nociceptors, for example, have been categorized by how quickly they conduct their signals, which is determined by the diameter of the fibers and whether they are myelinated or unmyelinated. (
  • Sensitization to suprathreshold mechanical stimuli was observed for both A- and C-fiber nociceptors, although it was greater for the A fibers. (
  • Heat sensitization was observed in 25% of A-fiber nociceptors, but the responses of C fibers to heat were depressed. (
  • Based on sensory thresholds and electrically induced activity-dependent slowing (ADS) of axonal conduction, C-fibers were classified as mechano-sensitive afferents, mechano-insensitive afferents, cold nociceptors, and sympathetic efferents. (
  • In nociception, intense chemical (e.g., cayenne powder), mechanical (e.g., cutting, crushing), or thermal (heat and cold) stimulation of sensory nerve cells called nociceptors produces a signal that travels along a chain of nerve fibers via the spinal cord to the brain. (
  • Nociceptors are the nerve endings responsible for nociception , one of the two types of persistent pain (the other, neuropathic pain , occurs when nerves in the central or peripheral nervous system are not functioning properly). (
  • Collectively, our data further support a role for Ca v 3.2 channels in peripheral nociception and identify a novel mechanism for Ca v 3.2 modulation that underlies nociceptor sensitization. (
  • Nociceptor-specific knockdown of EJC factors and eIFs resulted in defective thermal and mechanical nociception. (
  • No direct link was found between nociceptor dendritic morphology and nociception defects, which indicates that nociceptor morphology does not determine nociceptor sensitivity. (
  • In mammals, nociceptors are found in any area of the body that can sense noxious stimuli. (
  • The peripheral terminal of the mature nociceptor is where the noxious stimuli are detected and transduced into electrical energy. (
  • Here, we review the nociceptive aspect of pain perception, focusing on nociceptors innervating the skin and subserving exteroception of noxious stimuli. (
  • Since recent reviews have described in detail the molecules involved in detecting noxious stimuli ( 10 - 13 ) and contributing to protective mechanisms mediating enhanced pain at the site of injury ( 14 ), we take an integrative approach that highlights recently discovered cellular transduction/conduction mechanisms in the context of different nociceptor fiber types identified in vivo and ex vivo. (
  • Nociceptive pain occurs when nociceptors in the body detect noxious stimuli that have the potential to cause harm to the body. (
  • TRP channels that detect noxious stimuli (mechanical, thermal, and chemical pain) relay that info to nociceptors that generate an action potential. (
  • The present study suggests that the development of myelinated nociceptors is dependent on trkA and trkC but not on trkB. (
  • Therefore, we hypothesize that the SS-EPs elicited by the rapid periodic thermal activation of nociceptors may reflect the activation of a network that is preferentially involved in processing nociceptive input and may thus provide some important insight into the cortical processes generating painful percepts. (
  • Silent nociceptors must be first activated or 'awakened' by tissue inflammation before responding to a mechanical, thermal, or chemical stimulus. (
  • Adaptive pain is a normal response to nociceptor activation by a noxious stimulus that is intended to prevent tissue injury and/or promote healing of injured tissue. (
  • Multiple firing of C nociceptors upon a single electrical stimulus has been suggested to be a possible mechanism contributing to neuropathic pain. (
  • The high-energy nociceptive stimulus elicited a consistent SS-EP, related to the activation of A delta-nociceptors. (
  • Only when the high threshold has been reached by either chemical, thermal, or mechanical environments are the nociceptors triggered. (
  • Thermal nociceptors respond to extreme hot or cold temperatures. (
  • Thermal nociceptors are activated by noxious heat or cold, temperatures above 45°C and below 5°C (Kandel et al, 2000). (
  • We explored the hypothesis that differences in withdrawal behavior are mediated by differential expression of isoflurane-sensitive proteins between these types of thermal nociceptors. (
  • Identification and cloning of the VR1 channel represented a significant step in the clarification of the molecular mechanisms underlying transduction of noxious chemical and thermal stimuli by peripheral nociceptors ( 1 ). (
  • Potentially damaging mechanical, thermal, and chemical stimuli are detected by nerve endings called nociceptors, which are found in the skin, on internal surfaces such as the periosteum, joint surfaces, and in some internal organs. (
  • Here, we demonstrate that reducing agents as well as endogenous metal chelators sensitize C-type dorsal root ganglion nociceptors by chelating Zn 2+ ions off specific extracellular histidine residues on Ca v 3.2 T-channels, thus relieving tonic channel inhibition, enhancing Ca v 3.2 currents, and lowering the threshold for nociceptor excitability in vitro and in vivo . (
  • Collectively, these findings describe a novel mechanism of nociceptor sensitization and firmly establish reducing agents, as well as Zn 2+ , Zn 2+ -chelating amino acids, and Zn 2+ -chelating proteins as endogenous modulators of Ca v 3.2 and nociceptor excitability. (
  • Last, we show that reducing agents, as well as synthetic and endogenous Zn 2+ chelators, sensitize Ca v 3.2 current-containing C-type nociceptors from wild-type mice but not C-type nociceptors from Ca v 3.2 −/− mice in vitro and in vivo . (
  • Post-discharge hyperpolarization is an endogenous modulatory factor limiting input from fast-conducting nociceptors (AHTMRs). (
  • Our goal is to separate these functions for nociceptors in order to provide pain relief while also enabling or maintaining endogenous mechanisms of organ protection from ischemia-reperfusion injury. (
  • These findings are relevant to the physiological modulation of dental nociceptors by endogenous NPY and demonstrate an important novel analgesic target for the treatment of dental pain. (
  • The results of this study identify the physiological role of endogenous Ret signaling in the survival and function of nociceptors. (
  • Internal nociceptors are found in a variety of organs, such as the muscles, the joints, the bladder, the visceral organs, and the digestive tract. (
  • Most visceral nociceptors (those located on organs inside the body) are silent nociceptors. (
  • Human visceral nociceptor mechanosensitivity is also attenuated by tegaserod suggesting that its efficacy for the treatment of pain in IBS may be mediated through the reduction of visceral nociceptor mechanosensitivity. (
  • In vivo, more hyperpolarized C-nociceptor Ems were associated with higher cytoplasmic edge-TREK2 expression (edge-TREK2). (
  • In the present study, we sought to determine if anandamide excited cutaneous C nociceptors in vivo and if this excitation correlated with nocifensive behaviors. (
  • In addition, Ret-Na(v)1.8 CKO mice have increased sensitivity to cold and increased formalin-induced pain, demonstrating that Ret signaling modulates the function of nociceptors in vivo. (
  • Mechanically sensitive nociceptor afferents were studied in a preparation of isolated skin from rat leg. (
  • In addition to the type of stimuli a nociceptor responds to, nociceptors are also classified by how fast they transmit pain signals. (
  • We show here that conducting (sometimes called uninjured) C-nociceptors in neuropathic pain models with more hyperpolarized resting membrane potentials (Ems) have lower SF rates. (
  • The GFLs are analgesic in models of neuropathic pain emphasizing the importance of understanding the physiological function of GFL/Ret signaling in nociceptors. (
  • Critical role of nociceptor plasticity in chronic pain. (
  • This review will discuss current knowledge on the role of nociceptor thermoTRPs in pain and therapy and describes the activator and inhibitor molecules known to interact with them and modulate their activity. (
  • Peripheral sensitization of nociceptors has been demonstrated as a possible mechanism of vulvodynia. (
  • Importantly, we hypothesize that sensitization of nociceptors by opiates can occur in the absence of tissue injury. (
  • Other nociceptors respond to none of these modalities (although they may respond to stimulation under conditions of inflammation) and are referred to as sleeping or silent. (
  • Epineural optogenetic activation of nociceptors initiates and amplifies inflammation. (
  • inflammation of the plantar fascia, thickening of the proximal fascia, decreased vascularity, peritendinous inflammation, loss of normal elasticity, and alteration of nociceptor physiology all may play roles in the onset and persistence of heel pain. (
  • Other nociceptors respond to none of these modalities (although they may respond to stimulation under conditions of inflammation) and have thereby earned the more poetic title of sleeping or silent nociceptors (Kandel et al, 2000). (
  • Silent nociceptors do not usually fire action potentials , though they are much more likely to do so in the presence of inflammation or damaging chemicals (Kandel et al, 2000). (
  • EXPRESS] Upregulation of P2Y1 in neonatal nociceptors regulates heat and mechanical sensitization during cutaneous inflammation. (
  • We conclude that the rapid increase in the number of {alpha},{beta}-methylene ATP responsive nociceptors and the increased magnitude of the neural response following carrageenan inflammation explains why very low concentrations of such agonists can cause pain in inflammatory states. (
  • For a specific examination of nociceptor function, action potentials from single C-fibres including 214 C-nociceptors were recorded by microneurography. (
  • METHODS: We recorded action potentials from rat joint nociceptors after intraarticular injection of IL-17A. (
  • Besides this, a recent study demonstrated that onabotulinumtoxinA selectively inhibited C- but not Ad-trigeminal meningeal nociceptors by utilizing a preclinical cranial pain model (41). (
  • Exploring the effects of extracranial injections of botulinum toxin type A on prolonged intracranial meningeal nociceptors responses to cortical spreading depression in female rats. (
  • During migraine, CGRP is thought to be released from peripheral endings of perivascular meningeal nociceptors primary and to promote vasodilatation. (
  • Here, using electrophysiological, extracellular, single-unit recording combined with laser-Doppler flowmetry measurements of dural blood flow (DBF), we examined whether CGRP and meningeal vasodilatation promote activation or sensitization of meningeal nociceptors. (
  • however, neither method of CGRP administration resulted in activation or sensitization of meningeal nociceptors. (
  • The results of this study suggest that CGRP effects in the meninges, including meningeal vasodilatation, are not sufficient to activate or sensitize meningeal nociceptors. (
  • On the contrary, the peptidergic nociceptors continue to use TrkA, and they express a completely different type of growth factor. (
  • Our findings further imply a central role of αCGRP peptidergic nociceptors in peripheral algesic sensitization, and substantiate that inhibition of LDCVs exocytosis is a valuable therapeutic strategy to treat pain, as it concurrently reduces the release of pro-inflammatory peptides and the membrane recruitment of thermoTRP channels. (
  • More recent studies have analyzed the nerve factors, thermoreceptors, and nociceptors in women with vulvar pain. (
  • This exploratory analysis highlights the differing role that volatile anesthetics might have on nociceptors in the peripheral nervous system. (
  • Nociceptors Tolerance (BB CI 01) is a genetic mutation neuron located on the Neuronal menu. (
  • The Nociceptors Tolerance (BB CI 01) neuron is located on the Therapeutic Medication neuronal branch . (
  • 2017) showed that over a short testing period, initial PPT trials caused superficial nociceptors to have an increased sensitivity, resulting in higher PPT values. (
  • Currently, there are significant gaps in understanding of the regulatory mechanisms involved in nociceptor sensitivity. (
  • Dysregulated nociceptor sensitivity is the likely pathogenesis in many types of chronic pain, a disease that ails over 100 million people in the United States alone. (
  • The goal of this study was to characterize how genes classically involved in RNA processing and translation regulate nociceptor sensitivity. (
  • My results suggest that eukaryotic initiation factors (eIFs) and components of the exon junction complex (EJC) control nociceptor sensitivity by regulating RNA processing and translation, suggesting a major role for RNA metabolism and translation in controlling nociceptor function. (
  • Thus, the major findings of this project revealed that Drosophila nociceptor sensitivity is controlled by RNA processing mechanisms from transcription to translation. (
  • The activation of functionally distinct cutaneous nociceptor populations and the processing of information they convey provide a rich diversity of pain qualities. (
  • Nociceptors develop from neural-crest stem cells. (
  • The neural-crest stem cells split from the neural tube as it closes, and nociceptors grow from the dorsal part of this neural-crest tissue. (
  • CHIR99021, SU5402 and DAPT induce and accelerate neural crest stem cell identity by day 8 and promote rapid differentiation of the neural crest stem cells to nociceptors expressing peptidergic markers by day 10. (
  • Pain from excitation of identified muscle nociceptors in humans. (
  • We also determined whether excitation of C nociceptors by anandamide was associated with nocifensive behaviors. (
  • We investigated peripheral C-nociceptors in painful and painless polyneuropathy patients to identify pain-specific changes. (
  • Double spikes to single electrical stimulation correlates to spontaneous activity of nociceptors in painful neuropathy patients. (
  • We investigated painful neuropathy patients using microneurography and analysed nociceptors for the occurrence of multiple spiking and spontaneous activity. (
  • Multiple spiking of nociceptors coincides with spontaneous activity in nociceptors of painful neuropathy patients. (
  • Sensitisation: Increased intensity of nociceptor responses. (
  • Tensile and compressive responses of nociceptors in rat hairy skin. (
  • Single-fiber recordings were made from nociceptors in the sciatic nerve of barbiturate- anesthetized animals, and their responses compared with those obtained from nociceptors tested identically in normal animals. (
  • Bullfrogs (Rana catesbeiana) anesthetized with a large dose of thiopental (42.8 mg/kg) retained movement responses to nociceptor stimuli despite an average plasma drug level of 51 mg/l, of which 63% was bound to plasma proteins. (
  • The time course of {alpha},{beta}-methylene ATP-evoked discharges in nociceptors was found to correlate well with the time course of behavioural nocifensive responses in rats to the same agonist described in a previous study (Hamilton et al. (
  • 2. Both ATP and {alpha},{beta}-methylene ATP were found to specifically activate the peripheral terminals of A{delta} and C-fibre nociceptors in the skin. (
  • The nonpeptidergic nociceptors switch off the TrkA and begin expressing Ret, which is a transmembrane signaling component that allows the expression of glial-cell-derived growth factor (GDNF). (
  • The nonpeptidergic nociceptors switch off the TrkA and begin expressing Ret. (
  • The function of NGF/TrkA signaling in the TrkA population of nociceptors has been extensively studied, and NGF/TrkA signaling is a well established mediator of pain. (
  • The ability of fish to feel pain is sustained by the presence of nociceptors (delta A and C fibres) identical to those of mammals, connected to a comparative brain structure (Sneddon, 2003). (
  • The interval between the main action potential and the multiple spikes ranged from 13 to 100 ms. There was a significant association between spontaneous activity and multiple spiking in C nociceptors, with spontaneous activity being present in 9 of 11 fibres with multiple spiking, but only in 21 of 94 nociceptors without multiple spiking (P (
  • Another thermoTRP, TRPM8, encoding for the cool sensation and also expressed in nociceptors, has recently been shown to reduce pain via a central mechanism, thus opening a novel strategy for achieving analgesia. (
  • However, the molecular mechanisms underlying the functions of T-channels in nociceptors are poorly understood. (
  • Additionally, mechanisms underlying possible nociceptor sensitization occurring in the absence of tissue injury may ultimately lead to insights into clinical conditions of prominent pain without apparent tissue injury including, for example fibromyalgia, IBS, CRPS-1 and perhaps migraine. (
  • This is why taking pain medication, such as a nonsteroidal anti-inflammatory (NSAID), to block nociceptor activation is sensible when the 'pain alert' is being addressed. (
  • The omega-3 fatty acids in fish oil can decrease IL-6 and TNF-alpha, two inflammatory factors that angry up the aforementioned nociceptors. (
  • In 11 of 105 nociceptors, double spiking was found, with 1 fibre even showing triple spikes on electrical stimulation. (