Tetrodotoxin: 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.Pain: An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.Chronic Pain: Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain.Pain Management: A form of therapy that employs a coordinated and interdisciplinary approach for easing the suffering and improving the quality of life of those experiencing pain.Pain Threshold: Amount of stimulation required before the sensation of pain is experienced.Pain, Postoperative: Pain during the period after surgery.Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous SPRAINS AND STRAINS; INTERVERTEBRAL DISK DISPLACEMENT; and other conditions.Back Pain: Acute or chronic pain located in the posterior regions of the THORAX; LUMBOSACRAL REGION; or the adjacent regions.Pain Measurement: 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.Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region.Neck Pain: Discomfort or more intense forms of pain that are localized to the cervical region. This term generally refers to pain in the posterior or lateral regions of the neck.Pain, Intractable: Persistent pain that is refractory to some or all forms of treatment.Saxitoxin: A compound that contains a reduced purine ring system but is not biosynthetically related to the purine alkaloids. It is a poison found in certain edible mollusks at certain times; elaborated by GONYAULAX and consumed by mollusks, fishes, etc. without ill effects. It is neurotoxic and causes RESPIRATORY PARALYSIS and other effects in MAMMALS, known as paralytic SHELLFISH poisoning.Pelvic Pain: Pain in the pelvic region of genital and non-genital origin and of organic or psychogenic etiology. Frequent causes of pain are distension or contraction of hollow viscera, rapid stretching of the capsule of a solid organ, chemical irritation, tissue ischemia, and neuritis secondary to inflammatory, neoplastic, or fibrotic processes in adjacent organs. (Kase, Weingold & Gershenson: Principles and Practice of Clinical Gynecology, 2d ed, pp479-508)Pain Perception: The process by which PAIN is recognized and interpreted by the brain.Sodium Channel Blockers: 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.Facial Pain: Pain in the facial region including orofacial pain and craniofacial pain. Associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves. Conditions which feature recurrent or persistent facial pain as the primary manifestation of disease are referred to as FACIAL PAIN SYNDROMES.Acute Pain: Intensely discomforting, distressful, or agonizing sensation associated with trauma or disease, with well-defined location, character, and timing.Pain, Referred: A type of pain that is perceived in an area away from the site where the pain arises, such as facial pain caused by lesion of the VAGUS NERVE, or throat problem generating referred pain in the ear.Sodium Channels: 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.Veratridine: A benzoate-cevane found in VERATRUM and Schoenocaulon. It activates SODIUM CHANNELS to stay open longer than normal.Shoulder Pain: Unilateral or bilateral pain of the shoulder. It is often caused by physical activities such as work or sports participation, but may also be pathologic in origin.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Musculoskeletal Pain: Discomfort stemming from muscles, LIGAMENTS, tendons, and bones.Atropine: An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.Anesthetics, Local: Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate.Tetraodontiformes: A small order of primarily marine fish containing 340 species. Most have a rotund or box-like shape. TETRODOTOXIN is found in their liver and ovaries.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Fishes, PoisonousProtoveratrines: Mixtures of closely related hypotensive alkaloids from Veratrum album (Liliaceae). They have been used in the treatment of hypertension but have largely been replaced by drugs with fewer adverse effects.VeratrineLidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.Nociceptive Pain: Dull or sharp aching pain caused by stimulated NOCICEPTORS due to tissue injury, inflammation or diseases. It can be divided into somatic or tissue pain and VISCERAL PAIN.Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.Neurons: 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.Electrophysiology: 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.Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Rats, Sprague-Dawley: 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.Guanethidine: An antihypertensive agent that acts by inhibiting selectively transmission in post-ganglionic adrenergic nerves. It is believed to act mainly by preventing the release of norepinephrine at nerve endings and causes depletion of norepinephrine in peripheral sympathetic nerve terminals as well as in tissues.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.Tetraethylammonium CompoundsAnalgesics, Opioid: Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.Hexamethonium Compounds: Compounds containing the hexamethylenebis(trimethylammonium) cation. Members of this group frequently act as antihypertensive agents and selective ganglionic blocking agents.Hexamethonium: A nicotinic cholinergic antagonist often referred to as the prototypical ganglionic blocker. It is poorly absorbed from the gastrointestinal tract and does not cross the blood-brain barrier. It has been used for a variety of therapeutic purposes including hypertension but, like the other ganglionic blockers, it has been replaced by more specific drugs for most purposes, although it is widely used a research tool.Ileum: The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.Poisons: Substances which, when ingested, inhaled, or absorbed, or when applied to, injected into, or developed within the body in relatively small amounts may, by their chemical action, cause damage to structure or disturbance of function. (From Dorland, 27th ed)Time Factors: Elements of limited time intervals, contributing to particular results or situations.Myofascial Pain Syndromes: Muscular pain in numerous body regions that can be reproduced by pressure on TRIGGER POINTS, localized hardenings in skeletal muscle tissue. Pain is referred to a location distant from the trigger points. A prime example is the TEMPOROMANDIBULAR JOINT DYSFUNCTION SYNDROME.Hyperalgesia: 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.Patch-Clamp Techniques: 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.Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.Complex Regional Pain Syndromes: Conditions characterized by pain involving an extremity or other body region, HYPERESTHESIA, and localized autonomic dysfunction following injury to soft tissue or nerve. The pain is usually associated with ERYTHEMA; SKIN TEMPERATURE changes, abnormal sudomotor activity (i.e., changes in sweating due to altered sympathetic innervation) or edema. The degree of pain and other manifestations is out of proportion to that expected from the inciting event. Two subtypes of this condition have been described: type I; (REFLEX SYMPATHETIC DYSTROPHY) and type II; (CAUSALGIA). (From Pain 1995 Oct;63(1):127-33)Toxins, Biological: Specific, characterizable, poisonous chemicals, often PROTEINS, with specific biological properties, including immunogenicity, produced by microbes, higher plants (PLANTS, TOXIC), or ANIMALS.Chronic Disease: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)Visceral Pain: Pain originating from internal organs (VISCERA) associated with autonomic phenomena (PALLOR; SWEATING; NAUSEA; and VOMITING). It often becomes a REFERRED PAIN.Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016).Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Neurilemma: The outermost cytoplasmic layer of the SCHWANN CELLS covering NERVE FIBERS.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.Batrachotoxins: Batrachotoxin is the 20-alpha-bromobenzoate of batrachotoxin A; they are toxins from the venom of a small Colombian frog, Phyllobates aurotaenia, cause release of acetylcholine, destruction of synaptic vesicles and depolarization of nerve and muscle fibers.Anura: An order of the class Amphibia, which includes several families of frogs and toads. They are characterized by well developed hind limbs adapted for jumping, fused head and trunk and webbed toes. The term "toad" is ambiguous and is properly applied only to the family Bufonidae.Arthralgia: Pain in the joint.Marine Toxins: Toxic or poisonous substances elaborated by marine flora or fauna. They include also specific, characterized poisons or toxins for which there is no more specific heading, like those from poisonous FISHES.Nociceptors: 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.Rana esculenta: An edible species of the family Ranidae, occurring in Europe and used extensively in biomedical research. Commonly referred to as "edible frog".Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position.Gastrointestinal Motility: The motor activity of the GASTROINTESTINAL TRACT.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.NAV1.8 Voltage-Gated Sodium Channel: 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.Analgesia: Methods of PAIN relief that may be used with or in place of ANALGESICS.Neurotransmitter Agents: Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.Labor Pain: Pain associated with OBSTETRIC LABOR in CHILDBIRTH. It is caused primarily by UTERINE CONTRACTION as well as pressure on the CERVIX; BLADDER; and the GASTROINTESTINAL TRACT. Labor pain mostly occurs in the ABDOMEN; the GROIN; and the BACK.Decapodiformes: A superorder of CEPHALOPODS comprised of squid, cuttlefish, and their relatives. Their distinguishing feature is the modification of their fourth pair of arms into tentacles, resulting in 10 limbs.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Spinal Cord: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.Colon: The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.Aconitine: A C19 norditerpenoid alkaloid (DITERPENES) from the root of ACONITUM plants. It activates VOLTAGE-GATED SODIUM CHANNELS. It has been used to induce ARRHYTHMIAS in experimental animals and it has antiinflammatory and antineuralgic properties.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Nerve Block: Interruption of NEURAL CONDUCTION in peripheral nerves or nerve trunks by the injection of a local anesthetic agent (e.g., LIDOCAINE; PHENOL; BOTULINUM TOXINS) to manage or treat pain.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.Cnidarian Venoms: Venoms from jellyfish; CORALS; SEA ANEMONES; etc. They contain hemo-, cardio-, dermo- , and neuro-toxic substances and probably ENZYMES. They include palytoxin, sarcophine, and anthopleurine.Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.Conotoxins: Peptide neurotoxins from the marine fish-hunting snails of the genus CONUS. They contain 13 to 29 amino acids which are strongly basic and are highly cross-linked by disulfide bonds. There are three types of conotoxins, omega-, alpha-, and mu-. OMEGA-CONOTOXINS inhibit voltage-activated entry of calcium into the presynaptic membrane and therefore the release of ACETYLCHOLINE. Alpha-conotoxins inhibit the postsynaptic acetylcholine receptor. Mu-conotoxins prevent the generation of muscle action potentials. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)Capsaicin: An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.Neuromuscular Junction: The synapse between a neuron and a muscle.Myenteric Plexus: One of two ganglionated neural networks which together form the ENTERIC NERVOUS SYSTEM. The myenteric (Auerbach's) plexus is located between the longitudinal and circular muscle layers of the gut. Its neurons project to the circular muscle, to other myenteric ganglia, to submucosal ganglia, or directly to the epithelium, and play an important role in regulating and patterning gut motility. (From FASEB J 1989;3:127-38)Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Methysergide: An ergot derivative that is a congener of LYSERGIC ACID DIETHYLAMIDE. It antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. Methysergide is used prophylactically in migraine and other vascular headaches and to antagonize serotonin in the carcinoid syndrome.Muscles: Contractile tissue that produces movement in animals.Scorpion Venoms: Venoms from animals of the order Scorpionida of the class Arachnida. They contain neuro- and hemotoxins, enzymes, and various other factors that may release acetylcholine and catecholamines from nerve endings. Of the several protein toxins that have been characterized, most are immunogenic.Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)Cesium: A member of the alkali metals. It has an atomic symbol Cs, atomic number 50, and atomic weight 132.91. Cesium has many industrial applications, including the construction of atomic clocks based on its atomic vibrational frequency.Ganglia, Spinal: 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.6-Cyano-7-nitroquinoxaline-2,3-dione: A potent excitatory amino acid antagonist with a preference for non-NMDA iontropic receptors. It is used primarily as a research tool.GABA Antagonists: Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.Neural Conduction: The propagation of the NERVE IMPULSE along the nerve away from the site of an excitation stimulus.Evoked Potentials: Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported.Enteric Nervous System: Two ganglionated neural plexuses in the gut wall which form one of the three major divisions of the autonomic nervous system. The enteric nervous system innervates the gastrointestinal tract, the pancreas, and the gallbladder. It contains sensory neurons, interneurons, and motor neurons. Thus the circuitry can autonomously sense the tension and the chemical environment in the gut and regulate blood vessel tone, motility, secretions, and fluid transport. The system is itself governed by the central nervous system and receives both parasympathetic and sympathetic innervation. (From Kandel, Schwartz, and Jessel, Principles of Neural Science, 3d ed, p766)Voltage-Gated Sodium Channels: A family of membrane proteins that selectively conduct SODIUM ions due to changes in the TRANSMEMBRANE POTENTIAL DIFFERENCE. They typically have a multimeric structure with a core alpha subunit that defines the sodium channel subtype and several beta subunits that modulate sodium channel activity.Nerve Endings: Branch-like terminations of NERVE FIBERS, sensory or motor NEURONS. Endings of sensory neurons are the beginnings of afferent pathway to the CENTRAL NERVOUS SYSTEM. Endings of motor neurons are the terminals of axons at the muscle cells. Nerve endings which release neurotransmitters are called PRESYNAPTIC TERMINALS.Ranvier's Nodes: Regularly spaced gaps in the myelin sheaths of peripheral axons. Ranvier's nodes allow saltatory conduction, that is, jumping of impulses from node to node, which is faster and more energetically favorable than continuous conduction.Vasoactive Intestinal Peptide: A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors (RECEPTORS, VASOACTIVE INTESTINAL PEPTIDE).Neuromuscular Depolarizing Agents: Drugs that interrupt transmission at the skeletal neuromuscular junction by causing sustained depolarization of the motor end plate. These agents are primarily used as adjuvants in surgical anesthesia to cause skeletal muscle relaxation.Tubocurarine: A neuromuscular blocker and active ingredient in CURARE; plant based alkaloid of Menispermaceae.Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.Phentolamine: A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of RAYNAUD DISEASE and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease.Muscle Denervation: The resection or removal of the innervation of a muscle or muscle tissue.Fibromyalgia: A common nonarticular rheumatic syndrome characterized by myalgia and multiple points of focal muscle tenderness to palpation (trigger points). Muscle pain is typically aggravated by inactivity or exposure to cold. This condition is often associated with general symptoms, such as sleep disturbances, fatigue, stiffness, HEADACHES, and occasionally DEPRESSION. There is significant overlap between fibromyalgia and the chronic fatigue syndrome (FATIGUE SYNDROME, CHRONIC). Fibromyalgia may arise as a primary or secondary disease process. It is most frequent in females aged 20 to 50 years. (From Adams et al., Principles of Neurology, 6th ed, p1494-95)Questionnaires: Predetermined sets of questions used to collect data - clinical data, social status, occupational group, etc. The term is often applied to a self-completed survey instrument.Microelectrodes: Electrodes with an extremely small tip, used in a voltage clamp or other apparatus to stimulate or record bioelectric potentials of single cells intracellularly or extracellularly. (Dorland, 28th ed)Apamin: A highly neurotoxic polypeptide from the venom of the honey bee (Apis mellifera). It consists of 18 amino acids with two disulfide bridges and causes hyperexcitability resulting in convulsions and respiratory paralysis.4-Aminopyridine: One of the POTASSIUM CHANNEL BLOCKERS, with secondary effect on calcium currents, which is used mainly as a research tool and to characterize channel subtypes.Disability Evaluation: Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for Social Security and workmen's compensation benefits.Bupivacaine: A widely used local anesthetic agent.Catastrophization: Cognitive and emotional processes encompassing magnification of pain-related stimuli, feelings of helplessness, and a generally pessimistic orientation.Neurons, Afferent: Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM.Electrophorus: A genus of fish, in the family GYMNOTIFORMES, capable of producing an electric shock that immobilizes fish and other prey. The species Electrophorus electricus is also known as the electric eel, though it is not a true eel.Bicuculline: An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.NAV1.2 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion permeability of excitable membranes. Defects in the SCN2A gene which codes for the alpha subunit of this sodium channel are associated with benign familial infantile seizures type 3, and early infantile epileptic encephalopathy type 11.Neural Inhibition: The function of opposing or restraining the excitation of neurons or their target excitable cells.Physostigmine: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity.Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.Flank Pain: Pain emanating from below the RIBS and above the ILIUM.Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.Animals, Newborn: Refers to animals in the period of time just after birth.Crustacea: A large subphylum of mostly marine ARTHROPODS containing over 42,000 species. They include familiar arthropods such as lobsters (NEPHROPIDAE), crabs (BRACHYURA), shrimp (PENAEIDAE), and barnacles (THORACICA).Pleurobranchaea: A genus of side-gilled sea slugs in the family Pleurobranchidae, superorder GASTROPODA. They are opportunistic voracious feeders but prefer the sea anemone.Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates.Bethanechol: A slowly hydrolyzing muscarinic agonist with no nicotinic effects. Bethanechol is generally used to increase smooth muscle tone, as in the GI tract following abdominal surgery or in urinary retention in the absence of obstruction. It may cause hypotension, HEART RATE changes, and BRONCHIAL SPASM.Excitatory Postsynaptic Potentials: Depolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during neurotransmission. Excitatory postsynaptic potentials can singly or in summation reach the trigger threshold for ACTION POTENTIALS.Gastric Fundus: The superior portion of the body of the stomach above the level of the cardiac notch.Parasympathetic Nervous System: The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system.Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous.Eye Pain: A dull or sharp painful sensation associated with the outer or inner structures of the eyeball, having different causes.NAV1.7 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype found widely expressed in nociceptive primary sensory neurons. Defects in the SCN9A gene, which codes for the alpha subunit of this sodium channel, are associated with several pain sensation-related disorders.Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.Germine Acetates: Germine derivatives acetylated on any one or more of the hydroxy groups. These compounds are present in many polyester alkaloids which occur in Veratrum and Zygadenus species. They are used as antihypertensive agents, and in some cases, exhibit curare-like activity.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.omega-Conotoxin GVIA: A neurotoxic peptide, which is a cleavage product (VIa) of the omega-Conotoxin precursor protein contained in venom from the marine snail, CONUS geographus. It is an antagonist of CALCIUM CHANNELS, N-TYPE.Dimethylphenylpiperazinium Iodide: A selective nicotinic cholinergic agonist used as a research tool. DMPP activates nicotinic receptors in autonomic ganglia but has little effect at the neuromuscular junction.Tachyphylaxis: 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)Motor Neurons: Neurons which activate MUSCLE CELLS.Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.Potassium Chloride: A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx).Mollusca: A phylum of the kingdom Metazoa. Mollusca have soft, unsegmented bodies with an anterior head, a dorsal visceral mass, and a ventral foot. Most are encased in a protective calcareous shell. It includes the classes GASTROPODA; BIVALVIA; CEPHALOPODA; Aplacophora; Scaphopoda; Polyplacophora; and Monoplacophora.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Nitroarginine: An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6)Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.2-Amino-5-phosphonovalerate: The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors.QuinoxalinesTakifugu: A genus of pufferfish commonly used for research.Tachykinins: A family of biologically active peptides sharing a common conserved C-terminal sequence, -Phe-X-Gly-Leu-Met-NH2, where X is either an aromatic or a branched aliphatic amino acid. Members of this family have been found in mammals, amphibians, and mollusks. Tachykinins have diverse pharmacological actions in the central nervous system and the cardiovascular, genitourinary, respiratory, and gastrointestinal systems, as well as in glandular tissues. This diversity of activity is due to the existence of three or more subtypes of tachykinin receptors.Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to CADMIUM POISONING.Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis.Sodium Channel Agonists: A class of drugs that stimulate sodium influx through cell membrane channels.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Double-Blind Method: A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.Purkinje Fibers: Modified cardiac muscle fibers composing the terminal portion of the heart conduction system.Analgesics, Non-Narcotic: A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.Glycine Agents: Substances used for their pharmacological actions on glycinergic systems. Glycinergic agents include agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function.Scopolamine Hydrobromide: An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.Cats: The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Sensory Receptor Cells: 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.Nerve Fibers: 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.Ciguatoxins: Polycyclic ethers produced by Gambierdiscus (DINOFLAGELLATES) from gambiertoxins, which are ingested by fish which in turn may be ingested by humans who are susceptible to the CIGUATERA POISONING.Strychnine: An alkaloid found in the seeds of STRYCHNOS NUX-VOMICA. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison.Severity of Illness Index: Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder.N-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).Cholinergic Fibers: Nerve fibers liberating acetylcholine at the synapse after an impulse.Injections, Spinal: Introduction of therapeutic agents into the spinal region using a needle and syringe.Aminopyridines: Pyridines substituted in any position with an amino group. May be hydrogenated, but must retain at least one double bond.Urinary Bladder: A musculomembranous sac along the URINARY TRACT. URINE flows from the KIDNEYS into the bladder via the ureters (URETER), and is held there until URINATION.Mollusk Venoms: Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.Potassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.Neurokinin A: A mammalian neuropeptide of 10 amino acids that belongs to the tachykinin family. It is similar in structure and action to SUBSTANCE P and NEUROKININ B with the ability to excite neurons, dilate blood vessels, and contract smooth muscles, such as those in the BRONCHI.Oxocins: Compounds based on an 8-membered heterocyclic ring including an oxygen. They can be considered medium ring ethers.Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the TIBIAL NERVE and the PERONEAL NERVE.Muscarinic Antagonists: Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.Sciatica: A condition characterized by pain radiating from the back into the buttock and posterior/lateral aspects of the leg. Sciatica may be a manifestation of SCIATIC NEUROPATHY; RADICULOPATHY (involving the SPINAL NERVE ROOTS; L4, L5, S1, or S2, often associated with INTERVERTEBRAL DISK DISPLACEMENT); or lesions of the CAUDA EQUINA.Autonomic Fibers, Postganglionic: Nerve fibers which project from cell bodies of AUTONOMIC GANGLIA to SYNAPSES on target organs.Cevanes: Structurally-related alkaloids that contain the cevane carbon backbone.Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.
Khasar SG, Gold MS & Levine JD (1998). "A tetrodotoxin-resistant sodium current mediates inflammatory pain in the rat". ... Implications for mechanisms of pain". Pain. 131 (3): 243-57. doi:10.1016/j.pain.2007.07.026. PMC 2055547 . PMID 17766042. ... Nav1.7 thus been shown to be linked to human pain; Nav1.8, by contrast, had only been associated to pain in animal studies ... Therefore, Nav1.8 contributes to hyperalgesia (increased sensitivity to pain) and allodynia (pain from stimuli that do not ...
The root is traditionally used in Korea to treat chills in legs and arms and articular pain.[citation needed] In China, It has ... Aconitine is a potent neurotoxin that opens tetrodotoxin sensitive sodium channels. It increases influx of sodium through these ...
The use of Tetrodotoxin in leprosy (1912) Kawamura M et al. Chizei IIkai Jiho, 141. "On the leprosy settlement (Honmyoji buraku ... Chizei Ikai Jiho, 141.It was effective to some degree in neuralgic pain, but not effective in lepromatous leprosy. "On the ... The following were by Masayuki Kawamura: "The use of Tetrodotoxin in leprosy" (1912). Kawamura M et al. ...
"Tetrodotoxin for Moderate to Severe Cancer Pain: A Randomized, Double Blind, Parallel Design Multicenter Study". Journal of ... Multi-Dose Efficacy and Safety Study of Intramuscular Tetrodotoxin in Patients with Severe Cancer-Related Pain". Journal of ... Some dinotoxins are useful in pain management. These toxins may have potential therapeutic effects along with other medical ... Pain and Symptom Management. 35 (4): 420-429. doi:10.1016/j.jpainsymman.2007.05.011. Hagen, Neil A.; Fisher, Kim M.; Lapointe, ...
... multi-dose efficacy and safety study of intramuscular tetrodotoxin in patients with severe cancer-related pain". J Pain Symptom ... Tectin holds promise to relieve severe pain when other standard pain relievers are found to be ineffective. It is also being ... Tectin is the brand name of a pain killing drug currently in development by WEX Pharmaceuticals Inc. The drug is a purified ... The drug showed promising results in Canadian phase IIa clinical trials for the treatment of cancer related pain. However ...
... of tetrodotoxin-resistant sodium channels Nav1.8 and Nav1.9 within dorsal root ganglia in a rat model of bone cancer pain". ... The role of Nav1.9 in inflammatory and neuropathic pain has made it a potential drug target for pain relief. It is thought that ... Though most sodium channels are blocked by tetrodotoxin, Nav1.9 is tetrodotoxin-resistant due to the presence of serine on an ... The role of Nav1.9 in chronic inflammatory joint pain has been demonstrated in rat models of chronic inflammatory knee pain. ...
"Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling". The EMBO Journal. 31 (19): 3795-808. doi ... Brevetoxin Domoic acid Okadaic acid Saxitoxin Tetrodotoxin Vetter I, Touska F, Hess A, Hinsbey R, Sattler S, Lampert A, ...
Clinical studies have shown that 4-AP is capable of reversing the effects of tetrodotoxin poisoning in animals, however, its ... These improvements include sensory, motor and pulmonary function, with a decrease in spasticity and pain. Dalfampridine ... The drug has been shown to reverse saxitoxin and tetrodotoxin toxicity in tissue and animal experiments. Fampridine has been ... and tetrodotoxin (TTX)-induced cardiorespiratory depression in chronically instrumented guinea pigs". Fundamental and Applied ...
"First evidence of neosaxitoxin as a long-acting pain blocker in bladder pain syndrome". Int Urogynecol J. 26: 853-8. doi: ... Toxins such as neosaxitoxin and tetrodotoxin have less affinity for most cardiac Nav channels than for most Nav channels in ... Then, in cases of severe or prolonged pain, some patients need repeated injections, catheters, pumps and opioids to feel ... How CK, Chern CH, Huang YC, Wang LM, Lee CH (January 2003). "Tetrodotoxin poisoning". The American Journal of Emergency ...
Nav1.8 is a tetrodotoxin-resistant sodium channel that replaces lost sodium after cell damage. Increased expression of these ... ASIC1a is an acid-sensing ion channel involved in the pain sensory pathway, which is regulated by p11. Although the exact ...
Compared to the gold standard in pain management, morphine, epibatidine needed only 2.5 μg/kg to initiate a pain-relieving ... Arrow poison Batrachotoxin (and closely related Homobatrachotoxin) Tetrodotoxin Phantasmidine Fitch, R. W.; Spande, T. F.; ... "Epibatidine and pain" (PDF). British Journal of Anaesthesia 1998. pp. 69-76. Retrieved 2014-03-12. Clayton, S.C.; Regan, A.C. ... Mice became resistant to pain and heat with none of the negative effects of higher doses. Epibatidine most effectively enters ...
Because N-type voltage-dependent calcium channels are related to algesia (sensitivity to pain) in the nervous system, ω- ... a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels". J. Biol. Chem. 277 (30): 27247-55. doi:10.1074/ ... Prommer E (2006). "Ziconotide: a new option for refractory pain". Drugs Today. 42 (6): 369-78. doi:10.1358/dot.2006.42.6.973534 ...
Paroxysmal extreme pain disorder (PEPD) is another rare, extreme pain disorder. Like primary erythromelalgia, PEPD is similarly ... The Nav1.7 channel produces a rapidly activating and inactivating current which is sensitive to the level of tetrodotoxin. ... CS1 maint: Multiple names: authors list (link) "An SCN9A variant, known to cause pain, is now found to cause itch" (PDF). Pain ... Dib-Hajj SD, Cummins TR, Black JA, Waxman SG (November 2007). "From genes to pain: Nav1.7 and human pain disorders". Trends in ...
By some accounts, the frog is then held over or roasted alive over a fire until it cries in pain. Bubbles of poison form as the ... Tetrodotoxin, a toxin that works in the opposite way of batrachotoxin Daly, J. W.; Journal of the American Chemical Society ... When one of these frogs is agitated, feels threatened or is in pain, the toxin is reflexively released through several canals. ... While it is not an antidote, the membrane depolarization can be prevented or reversed by either tetrodotoxin (from puffer fish ...
Effects of epidural administration of HWTX-I in rats with chronic neuropathic pain. Chin J Pain Med. 2002;8:219-24. Wen Tao Z, ... Peng K, Shu Q, Liu Z, Liang S. Function and solution structure of huwentoxin-IV, a potent neuronal tetrodotoxin (TTX)-sensitive ... HWTX-I can relieve pain in the inflammatory joints and eliminate arthrocele to some degree. In a rat model of rheumatoid ... With HWTX-IV selectively blocking TTX-sensitive voltage-gated Na+ channels (which are involved in the pain pathways), it is ...
Palmer later broke silence to say he was heartbroken over the pain he had caused his dental staff. People for the Ethical ... In the middle is the blowfish (fugu) that can kill animals with its toxic organs that contain tetrodotoxin. The largest animal ... The killing of animals is animal euthanasia (for pain relief), animal sacrifice (for a deity), animal slaughter (for food), ... to reduce the pain felt by the animal and exsanguinate it at the same time. Tza'ar ba'alei chayim (literally means: "the ...
... pain therapy can also reduce harmful physiological consequences of untreated pain. Acute pain can often be managed using ... 1] Unlike cocaine produced local anesthetics which are intracellular in effect, saxitoxin, neosaxitoxin & tetrodotoxin bind to ... However, conduction anesthesia may be preferable because of superior pain control and fewer side effects. For purposes of pain ... Some typical uses of conduction anesthesia for acute pain are: Labor pain (epidural anesthesia, pudendal nerve blocks) ...
Drugs such as tetrodotoxin that block neural activity are typically lethal. Drugs targeting the neurotransmitter of major ... Descending NE fibers modulate afferent pain signals. ... The locus ceruleus (LC), which is located on the floor of the fourth ... this action mediates their euphoriant and pain relieving properties. Indirect agonists increase the binding of ...
The symptoms for diarrhetic shellfish poisoning include intense diarrhea and severe abdominal pains, and rarely nausea and ... Canadian Reference Materials Brevetoxin Ciguatoxin Domoic acid Saxitoxin Tetrodotoxin Reguera, B.; Riobo, P.; Rodriguez, F.; ...
If no signs of pain can be elicited, surgery should be performed within 24 hours of the incident, to remove the disc material ... A well-known example is the tetrodotoxin of fish species such as Takifugu rubripes, the famously lethal pufferfish of Japanese ... is voluntary restriction or inhibition of motion because of pain, incoordination, orgasm, or other cause, and is not due to ...
Meyer, Michael D. (2006). "Neuronal nicotinic acetylcholine receptors as a target for the treatment of neuropathic pain". Drug ... "First occurrence of tetrodotoxin in a dendrobatid frog (Colostethus inguinalis), with further reports for the bufonid genus ... Decker, M.; Meyer, M.; Sullivan, J. (2001). "The therapeutic potential of nicotinic acetylcholine receptor agonists for pain ...
Tetrodotoxin blocks action potentials in nerves by binding to the voltage-gated, fast sodium channels in nerve cell membranes, ... These sensory irritants produce immediate pain to the eyes and irritate mucous membranes (aka lachrymatory agent or lachrymator ... A separate class of nerve agents are related to Tetrodotoxin, frequently abbreviated as TTX, is a potent neurotoxin with no ... VE VG VM VX These agents are related to the puffer fish Tetrodotoxin Saxitoxin (TZ) Botulinum toxin. ...
Some viral causes may also be associated with fever, fatigue, headache, and muscle pain. If the stool is bloody, the cause is ... tetrodotoxin poisoning from the consumption of puffer fish among others, and botulism typically due to improperly preserved ... Tytgat GN (2007). "Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping and pain". Drugs. 67 (9): ... Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of energy, and dehydration may also occur. This ...
Martz, Lauren (2014). "Nav-i-gating antibodies for pain". Science-Business eXchange. 7 (23). doi:10.1038/scibx.2014.662. ISSN ... Tetrodotoxin (TTX). Intracellular[edit]. Drugs which block sodium channels by blocking from the intracellular side of the ... "J Pain. 8 (4): 315-24. doi:10.1016/j.jpain.2006.10.001. PMID 17175203.. ... Stephen McMahon; Martin Koltzenburg; Irene Tracey; Dennis C. Turk (1 March 2013). Wall & Melzack's Textbook of Pain: Expert ...
"What makes blue-rings so deadly? Blue-ringed octopus have tetrodotoxin". The Cephalopod Page. Retrieved 12 April 2017.. ... Animal welfare groups have objected to this practice on the basis that octopuses can experience pain.[145] Octopuses have a ... It contains tetrodotoxin, which causes paralysis by blocking the transmission of nerve impulses to the muscles. This causes ...
Jensen TS (2002). "Anticonvulsants in neuropathic pain: rationale and clinical evidence". European Journal of Pain. 6 Suppl A: ... Backonja M (June 2004). "Neuromodulating drugs for the symptomatic treatment of neuropathic pain". Current Pain and Headache ... Wiffen PJ, Derry S, Moore RA (December 2013). "Lamotrigine for chronic neuropathic pain and fibromyalgia in adults". The ... and reducing neuropathic pain,[26][27][28] although a systematic review conducted in 2013 concluded that well-designed clinical ...
The journal welcomes submissions in the areas of chronic pain, anaesthesia, dentistry and oral medicine, rheumatology, and drug ... studies focusing on laboratory and clinical findings in the field of pain research and the prevention and management of pain. ... Pain Research and Management is a peer-reviewed, Open Access journal that publishes original research articles, review articles ... decrease in mean pain intensity (for worst pain, average pain, or most bothersome pain) or a decrease of ≥50% of opioid ...
Pain. Neurologic Manifestations. Nervous System Diseases. Neuromuscular Diseases. Signs and Symptoms. Tetrodotoxin. Anesthetics ... The Purpose of This Study is to Determine if Tetrodotoxin (TTX) is Effective in the Treatment of Pain Resulting From ... Experimental: Max dose Tetrodotoxin (once daily) Max dose Tetrodotoxin injectable (1 ml volume), once a day in the morning for ... Experimental: Low dose Tetrodotoxin (twice daily) Low dose Tetrodotoxin injectable (1 ml volume), twice a day for four ...
Tetrodotoxin from fugu pufferfish can cause deadly poisoning, but delivered properly, it becomes a potent local anesthetic. ... In small amounts, they could provide potent pain relief, blocking the sodium channels that conduct pain messages, he says. ... For the new study, the team chose tetrodotoxin, a potent, commercially available compound derived from pufferfish. Tetrodotoxin ... While conventional local anesthetics block pain very effectively, they wear off quickly and can affect the heart and brain. ...
Safety & Efficacy Study of Subcutaneous Tetrodotoxin for Moderate to Severe Inadequately Controlled Cancer-related Pain. *Pain ... The Purpose of This Study is to Determine if Tetrodotoxin (TTX) is Effective in the Treatment of Pain Resulting From ... Efficacy: long-term efficacy of tetrodotoxin (TTX) in reducing pain and improving quality of life. Safety: long-term safety and ... The period of onset of pain response as reported by responders.. *The number of days a subject meets the definition of pain ...
Taming Tetrodotoxin June 13, 2019. Search for opioid alternatives explores pufferfish venom for precise painkilling ... Neuropathic pain is a hard-to-treat chronic pain condition caused by nervous system damage. For people affected, the lightest ... Influencing pain volume from above. Woolf, He and colleagues combined a mouse model of neuropathic pain with recently developed ... When the spinal neurons that are supposed to be pain-only send this information to the brain, we feel pain." ...
The present study tested the effect of hypotonicity on tetrodotoxin-sensitive sodium current (TTX-S current) in cultured ... From: Hypotonicity modulates tetrodotoxin-sensitive sodium current in trigeminal ganglion neurons. Contact corresponding author ...
In this study, we determined the possible difference in tetrodotoxin-sensitive (TTX-S) and -resistant (TTX-R) Na+ channel ... and CGRP within rat DRG neurons during acute incisional pain.. *Ke Ma, Quan-Hong Zhou, Jin Chen, Dong-Ping Du, Yonghua Ji, Wei ... Tetrodotoxin-sensitive and -resistant Na+ channel currents in subsets of small sensory neurons of rats.. @article{ ... In this study, we determined the possible difference in tetrodotoxin-sensitive (TTX-S) and -resistant (TTX-R) Na+ channel ...
... tetrodotoxin-sensitive, TTXs) and those resistant to all but micromolar concentrations of tetrodotoxin (tetrodotoxin- resistant ... Inflammatory pain manifests as spontaneous pain and pain hypersensitivity. Spontaneous pain reflects direct activation of ... tetrodotoxin;. TTXr,. TTX-resistant;. TTXs,. TTX-sensitive;. BDNF,. brain-derived neurotrophic factor;. AMPA,. α-amino-3- ... where the specific link between a noxious stimulus and pain is lost and pain can be produced by normally innocuous inputs (2, ...
TTX, formulated as Tectin, is in phase III clinical trials as an injectable systemic analgesic for chronic cancer pain. Here, ... Previous studies showed that in rats, combinations of tetrodotoxin (TTX) with bupivacaine had supra-additive effects on sciatic ... Tetrodotoxin for moderate to severe cancer pain: a randomized, double blind, parallel design multicenter study.. *Neil A Hagen ... An open-label, multi-dose efficacy and safety study of intramuscular tetrodotoxin in patients with severe cancer-related pain. ...
Drug Profile: Tetrodotoxin / TTX. 7.24. Drug Profile: Ubrogepant / MK-1602. 7.25. Drug Profile: YHD1119 / PREGABALIN. 8. ... Classification of Pain. 3.2.1. Acute Pain. 3.2.2. Chronic Pain. 3.2.2.1. Classification of Chronic Pain. 3.2.2.2. Chronic Pain ... Pain Management. 3.3.1. Therapeutics for Pain Management. 3.3.2. Devices for Pain Management. 3.3.3. Other Therapeutic ... Devices for Pain Management: Database. 8.3. Devices for Pain Management: Database Analysis. 8.3.1. Analysis by Type of Devices ...
1999) The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nat Neurosci 2:541-548. ... 1998) A tetrodotoxin-resistant sodium current mediates inflammatory pain in the rat. Neurosci Lett 256:17-20. ... 3D,E). Spontaneous pain evoked by inflammation was much reduced (Fig. 3F). Neuropathic pain, which does not require Nav1.8+ ... 1990) A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 43:205-218. ...
Tetrodotoxin Poisoning Associated With Eating Puffer Fish Transported from Japan -- California, 1996 ... Other manifestations include salivation, muscle twitching, diaphoresis, pleuritic chest pain, dysphagia, aphonia, and ... also possess tetrodotoxin in lethal quantities (3) (Table 1). Tetrodotoxin is heat-stable and blocks sodium conductance and ... Tetrodotoxin Poisoning Associated With Eating Puffer Fish Transported from Japan -- California, 1996 MMWR 45(19);389-391 ...
After receiving it for 4 days, some patients have reported pain relief for up to 2 weeks." Tetrodotoxins side effects have ... The Pain Patient Pain sensation is highly subjective, and individual pain threshold levels differ. Accurate assessment ... Tetrodotoxin Tetrodotoxin (Tectin) is derived from the neurotoxin of the puffer fish (the fish used in fugu sushi; Table 317) ... As understanding of pains etiology broadens, so too will treatment strategies. While many patients dream of a pain-free future ...
... tetrodotoxin, a deadly neurotoxin. Its pain-killing effects are 160,000 times stronger than cocaine. Eating the fish can give ... One of their many effects is that of a pain-killer - far stronger than cocaine. Boccaccios medieval tale, the Decameron, tells ... you a gentle physical tingle from the tetrodotoxin - and in Japan, the chefs who prepare fugo have to be licensed by the ...
In tiny doses, the pufferfishs tetrodotoxin can be turned into a pain-relieving ion channel blocker.. Jan 1, 2018. Kerry Grens ... It takes only a milligram of tetrodotoxin (TTX) from improperly prepared fugu-typically made from one of a number of genera of ... Read about other animal groups researchers are exploring for pain-killing leads in the full feature story, "Animal Analgesics." ... Its blocking pain from ever getting to the brain.-Christopher Gallen, Wex Pharmaceuticals ...
... and tetrodotoxin-resistant (TTXR) voltage-gated sodium channels (VGSC) in rat dorsal root ganglion neurons. Veratridine... ... The effects of veratridine have been compared on tetrodotoxin-sensitive (TTXS) ... Sodium channel Dorsal root ganglion Veratridine Tetrodotoxin Sensory neuron Pain This is a preview of subscription content, log ... A comparison of the effects of veratridine on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in isolated rat ...
Tetrodotoxin has also proved useful in the treatment of pain (originally used in Japan in the 1930s) from such diverse ... Tetrodotoxin sources in nature. Tetrodotoxin has also been isolated from widely differing animal species, including western ... ca:Tetradotoxina cs:Tetrodotoxin da:Tetradotoxin de:Tetrodotoxin hy:Տետրոդոտոքսին it:Tetradotossina nl:Tetrodotoxine sv: ... Geographic frequency of tetrodotoxin toxicity. Poisonings from tetrodotoxin have been almost exclusively associated with the ...
... tetrodotoxin explanation free. What is tetrodotoxin? Meaning of tetrodotoxin medical term. What does tetrodotoxin mean? ... Looking for online definition of tetrodotoxin in the Medical Dictionary? ... Nearly three-fourths of the patients said their pain was noticeably reduced during the tetrodotoxin test, and two patients ... tetrodotoxin. Also found in: Dictionary, Thesaurus, Acronyms, Encyclopedia, Wikipedia. tetrodotoxin. [tet´ro-do-tok″sin] a ...
Tetrodotoxin found in pufferfish can provide potent pain relief when given properly Opioids remain a mainstay of treatment for ... New review suggests solutions that can help ease chronic pain in women Women often suffer silently when in pain, whether its ... reflecting success in efforts to promote a multimodal approach to pain management (using a variety of methods to manage pain) ... New pain management technique can reduce loss of muscle strength in ACL knee surgery patients Anesthesiologists can ...
Effects of Tetrodotoxin in Mouse Models of Visceral Pain. Marine drugs 15 6. 2017 doi:10.3390/md15060188 ... PAIN, 152(6), 1238 - 1248. doi:10.1016/j.pain.2010.12.031. 2010. *Zhao J, Lee MC, Momin A, Cendan CM, Shepherd ST, Baker MD, ... PAIN, 152(3), S16 - S19. doi:10.1016/j.pain.2010.12.018. *Gaveriaux-Ruff C, Nozaki C, Nadal X, Hever XC, Weibel R, Matifas A, ... Salomons, T. V., Iannetti, G. D., Liang, M., & Wood, J. N. (2016). The "Pain Matrix" in Pain-Free Individuals. JAMA NEUROLOGY, ...
Khasar SG, Gold MS & Levine JD (1998). "A tetrodotoxin-resistant sodium current mediates inflammatory pain in the rat". ... Implications for mechanisms of pain". Pain. 131 (3): 243-57. doi:10.1016/j.pain.2007.07.026. PMC 2055547 . PMID 17766042. ... Nav1.7 thus been shown to be linked to human pain; Nav1.8, by contrast, had only been associated to pain in animal studies ... Therefore, Nav1.8 contributes to hyperalgesia (increased sensitivity to pain) and allodynia (pain from stimuli that do not ...
Tetrodotoxin (TTX) as a Therapeutic Agent for Pain. Choose your preferred view mode. Please select whether you prefer to view ...
2001) Effects of adrenergic agonists and antagonists on tetrodotoxin-induced nerve block. Reg Anesth Pain Med 26:239-245. ... 2003) Prolonged duration local anesthesia from tetrodotoxin-enhanced local anesthetic microspheres. Pain 104:415-421. ... 1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16:109-110. ... Also, none of the animals developed autotomy (self-injury) of their hindpaws (24), a behavior associated with pain (although ...
The root is traditionally used in Korea to treat chills in legs and arms and articular pain.[citation needed] In China, It has ... Aconitine is a potent neurotoxin that opens tetrodotoxin sensitive sodium channels. It increases influx of sodium through these ...
The spinal nerve ligation (SNL) model was used to determine the contribution of miR-30b to neuropathic pain, to evaluate ... These data suggest that miR-30b is involved in the development of neuropathic pain, probably by regulating the expression of ... The spinal nerve ligation (SNL) model was used to determine the contribution of miR-30b to neuropathic pain, to evaluate ... These data suggest that miR-30b is involved in the development of neuropathic pain, probably by regulating the expression of ...
  • Clinical trials have been ongoing to evaluate the analgesic effect of TTX in cancer pain [ 5 - 8 ]. (hindawi.com)
  • Pain is also, of course, a major clinical problem. (pnas.org)
  • Clinical pain is an expression, then, of plasticity in the somatosensory system, operating at multiple sites and due to diverse mechanisms. (pnas.org)
  • Tetrodotoxin poisoning: a clinical analysis, role of neostigmine and short-term outcome of 53 cases. (semanticscholar.org)
  • The report also features a detailed overview of the devices that are used for the treatment / management of pain associated with chronic clinical conditions. (globenewswire.com)
  • Such devices are increasingly being used to treat a variety of clinical conditions that are characterized by chronic pain and offer the convenience of being used in the homecare setting as well. (globenewswire.com)
  • Table 3 17 ) and is currently in clinical trials in Canada and Europe for the treatment of severe, refractory cancer pain. (pharmacytimes.com)
  • Vancouver-based Wex Pharmaceuticals is pursuing advanced clinical trials using TTX, which it harvests from the ovaries of the oblong blowfish ( Takifugu oblongus ), to treat cancer- and chemotherapy-related pain. (the-scientist.com)
  • A presumptive diagnosis of tetrodotoxin poisoning in all three men was based on clinical presentation in the ED and the history of recent consumption of fugu. (cdc.gov)
  • VANCOUVER, BRITISH COLUMBIA--(Marketwire - July 25, 2008) - WEX Pharmaceuticals Inc. ("WEX" or the "Company") (TSX:WXI) announced today that Dr. Neil Hagen, the lead investigator for WEX's Phase III clinical trial of TTX, will make a presentation titled "Tetrodotoxin (TTX): From Poison to Medicine" at the IXth World Conference on Clinical Pharmacology and Therapeutics in Quebec City, Quebec on July 28. (redorbit.com)
  • WEX recently started a Phase III clinical trial of TTX for the treatment of cancer pain. (redorbit.com)
  • This clinical trial (TEC-006) is a multicentre, randomized, double-blind and placebo-controlled trial comparing the efficacy and safety of TTX to placebo in approximately 120 patients with moderate to severe inadequately controlled cancer- related pain. (redorbit.com)
  • In this review, we describe the current knowledge of µ-CTX interacting with the different sodium channels subtypes, the mechanism of action and their potential therapeutic use as analgesic compounds in the clinical management of pain conditions. (mdpi.com)
  • A diagnosis of tetrodotoxin (TTX) poisoning was suggested by typical clinical manifestations and temporal proximity to consumption of TTX-containing fish. (hindawi.com)
  • Despite a lack of success in clinical trials of anti-TNF-α therapy in alleviating the sciatic type of neuropathic pain, the intricate link of TNF-α with other neuro-inflammatory signaling systems (e.g., chemokines and p38 MAPK) has indeed inspired a systems approach perspective for future drug development in treating neuropathic pain. (biomedcentral.com)
  • But the drug derived from the poison, tetrodotoxin, has already passed two phases of clinical tests, and doctors conducting early surveys say it eased pain in terminally ill cancer patients, where no other pain medication had worked. (shroomery.org)
  • Because pain is a subjective sensation, it is difficult to evaluate objectively in clinical trials. (yahoo.com)
  • We report three different clinical presentations of the I228M Na V 1.7 variant: presentation with severe facial pain, presentation with distal (feet, hands) pain, and presentation with scalp discomfort in three patients housing this Na V 1.7 variant, two of which are from a single family. (pubmedcentralcanada.ca)
  • WEX Pharmaceuticals Inc (WEX) is a clinical stage biotechnology company that focuses on the discovery, development, manufacture and commercialization of innovative drugs for pain management. (marketpublishers.com)
  • Signed into law by then-President Bill Clinton and sponsored by the American Academy of Pain Medicine, this mandate is intended to stimulate progress into pain research, education, and clinical management. (rutgers.edu)
  • Identified in just the past few years, ion channels such as VR1, P2X3, and TTX-resistant sodium channels represent promising targets for highly selective local anesthetics and analgesics for treating a variety of clinical pain conditions, according to Basbaum. (rutgers.edu)
  • WEX Pharmaceuticals Inc ., a Vancouver-based Canadian biotechnology company, has been working on clinical trials to use Tetrodotoxin (TTX) as an analgesic for the treatment of moderate to severe cancer-related pain. (digitaljournal.com)
  • My clinical and research activities are focused on modalities to reduce acute, procedural and postoperative pain in children. (childrenshospital.org)
  • This has involved clinical research with the intravenous nonsteroidal medication, ketorolac, evaluating its safety and efficacy as well as its effect on bladder hyperreactivity (bladder spasms) after urologic surgery and the development of new treatment modalities to reduce diffuse abdominal and shoulder pain after laparoscopic surgery. (childrenshospital.org)
  • Chronic widespread pain is a complex clinical problem. (plos.org)
  • The manifestation of pain in response to experimental stimuli such as skin heating, or to clinical pathologies such as joint degeneration, is known to vary markedly. (plos.org)
  • Chronic neuropathic pain, typically caused by damage to or a dysfunction of the peripheral or central nervous system, remains a major clinical problem and therapeutic challenge. (aspetjournals.org)
  • Evidence in support of a role of VGSCs in a variety of pain states obtained with pre-clinical, largely rodent models, has been confirmed in pain patients. (elifesciences.org)
  • Anand KJ (1998) Clinical importance of pain and stress in preterm neonates. (springer.com)
  • In fact a synthetic form of conotoxin (ziconotide), a blocker of N-type calcium channel was approved for clinical management of chronic pain. (moleculardevices.com)
  • Dublin, Sept. 25, 2018 (GLOBE NEWSWIRE) -- The "Non-Opioid Drugs for Chronic Pain and Pain Management Devices Market, 2018-2025" report has been added to ResearchAndMarkets.com's offering. (globenewswire.com)
  • The opioid crisis has prompted drug manufacturers to develop non-addictive, non-narcotic-based therapeutics / analgesics for the management of pain. (globenewswire.com)
  • As the opioid epidemic continues to claim lives and shatter families across the nation, a Cedars-Sinai expert is urging physicians and patients to try managing pain without the addictive pills. (news-medical.net)
  • Contrary to what some studies may suggest, the local anesthetic drug, liposomal bupivacaine, did not reduce in-hospital opioid prescriptions or opioid-related complications in patients who received the drug during total knee replacement surgery as part of a multimodal approach to manage postsurgical pain, finds a new study published in the Online First edition of Anesthesiology, the peer-reviewed medical journal of the American Society of Anesthesiologists. (news-medical.net)
  • Opioid use in patients recovering from hip and knee replacement decreased by one-third between 2006 and 2014, reflecting success in efforts to promote a multimodal approach to pain management (using a variety of methods to manage pain) rather than using opioids alone, reveals new research being presented at the ANESTHESIOLOGY 2017 annual meeting. (news-medical.net)
  • Now, researchers at Boston Children's Hospital are eyeing the fish's poison as a potential new anesthetic that could one day replace opioid pain drugs with all their flaws. (bostonglobe.com)
  • The balance of pronociceptive (pain-promoting) serotonin signaling mediated by the 5-HT 4 receptor and antinociceptive (pain-relieving) opioid signaling mediated by the mu opioid receptor (MOR) was altered. (sciencemag.org)
  • Devices such as implanted pumps are used for the delivery of drugs such as opioids intrathecally (introduction into spinal subarachnoid space by lumbar puncture) in patients with cancer pain.The wide variety of drugs in development includes opioid receptor ligands, bradykinin antagonists, mPGES-1 inhibitors, glutamate receptor antagonists, substance P and neurokinin receptor antagonists, norepinephrine transporter inhibitors, P2X2 neuron receptor antagonists and nitric oxide-based analgesics. (yahoo.com)
  • The company develops a new class of non-opioid analgesics utilizing its proprietary platform technology TTX (Tetrodotoxin or TTX). (marketpublishers.com)
  • The Centers for Disease Control and Prevention have called for a minimization in opioid prescription and use for chronic pain conditions, and thus, it is imperative to discover alternative non-opioid based strategies. (elsevier.com)
  • Studying cone snail venom has yielded novel pain pathways, but the peptides that function as toxins are difficult to translate into drugs. (the-scientist.com)
  • Here we report the cryo-EM structures of the human Nav1.7-beta1-beta2 complex bound to two combinations of pore blockers and gating modifier toxins (GMTs), tetrodotoxin with Protoxin-II and saxitoxin with Huwentoxin-IV, both determined at overall resolutions of 3.2 A. The two structures are nearly identical except for minor shifts of VSDII, whose S3-S4 linker accommodates the two GMTs in a similar manner. (proteopedia.org)
  • The global market for pain therapeutics used in cancer patients was approximately US$15.2 billion in 2005 and this is expected to reach at least US$23 billion by 2010. (redorbit.com)
  • Current work in this field is providing researchers with a more thorough understanding of nociceptor cell biology at molecular and systems levels and insight that will allow the targeted design of novel pain therapeutics. (jci.org)
  • Dublin, Oct. 30, 2020 (GLOBE NEWSWIRE) -- The 'Pain Therapeutics - Drugs, Markets and Companies' report from Jain PharmaBiotech has been added to ResearchAndMarkets.com's offering.The worldwide analgesic markets were analyzed for the year 2019 and projected to 2029. (yahoo.com)
  • Over 500 companies have been identified to be involved in developing or marketing pain therapeutics and 173 of these are profiled in the report along with 156 collaborations. (yahoo.com)
  • DUBLIN , May 23, 2019 /PRNewswire/ -- The "Pain Therapeutics - Drugs, Markets and Companies" report from Jain PharmaBiotech has been added to ResearchAndMarkets.com's offering. (ptcommunity.com)
  • The venom they naturally produce isn't that powerful, but the tetrodotoxin from the bacteria blocks the transmission of nerve impulses to muscles, and the diaphragm paralyses, causing suffocation. (nhm.ac.uk)
  • TTX may provide clinically meaningful analgesia for patients who have persistent moderate to severe cancer pain despite best analgesic care. (hindawi.com)
  • Tetrodotoxin is extremely potent, and much lower dosages are needed to produce an analgesic effect than with other drugs. (redorbit.com)
  • In hospitalized patients, 79% experience pain, with 46% experiencing severe pain despite analgesic therapy. (redorbit.com)
  • Mendelian heritable pain disorders have provided insights into human pain mechanisms and suggested new analgesic drug targets. (jci.org)
  • Fish-derived tetrodotoxin was initially focused on an indication of opiate addiction withdrawal but is found to have an analgesic action as well. (yahoo.com)
  • Minocycline is a widely used glial activation inhibitor that could suppress pain-related behaviors in a number of different pain animal models, yet, its analgesic mechanisms are not fully understood. (nih.gov)
  • These channels are currently regarded as being amongst the best validated targets for pain therapy and in particular have caught widespread attention following the discovery of the remarkable analgesic phenotype associated with the loss-of-function NaV1.7 mutations in humans. (uclb.com)
  • 6 Therefore, inhibition of NaV1.8 emerges as an attractive mechanism-based therapy for peripheral and visceral pain of neuropathic and inflammatory origin. (asahq.org)
  • Visceral pain occurred in 47% of patients during the first five years and was reported by 62% of patients at 15 years. (practicalpainmanagement.com)
  • The mechanism of visceral pain is still less understood compared with that of somatic pain. (springer.com)
  • This is primarily due to the diverse nature of visceral pain compounded by multiple factors such as sexual dimorphism, psychological stress, genetic trait, and the nature of predisposed disease. (springer.com)
  • With reports emerging about the varieties of peptide molecules involved in the pathological conditions of visceral pain, it is expected that better therapy will be achieved relatively soon to manage chronic visceral pain. (springer.com)
  • Astrocyte compensation of the defective ATPase in the cingulate cortex rescued glutamate uptake, prevented abnormal NMDA spikes, and reduced sensitivity to cranial pain triggers. (sciencemag.org)
  • The Nav1.7 and Nav1.8 subunits have emerged as key molecules involved in peripheral pain processing and in the development of an increased pain sensitivity associated with inflammation and tissue injury. (springer.com)
  • Identification of Na v 1.7 as responsible for the absence of pain sensitivity in humans has prompted the investigation of drugs targeting this channel as pain relievers. (sciencemag.org)
  • Sensitivity to pain varies considerably between individuals and is known to be heritable. (plos.org)
  • Increased sensitivity to experimental pain is a risk factor for developing chronic pain, a common and debilitating but poorly understood symptom. (plos.org)
  • 5%) influencing pain sensitivity, we explored the genetic variation in individuals' responses to experimental pain. (plos.org)
  • Quantitative sensory testing to heat pain was performed in 2,500 volunteers from TwinsUK (TUK): exome sequencing to a depth of 70× was carried out on DNA from singletons at the high and low ends of the heat pain sensitivity distribution in two separate subsamples. (plos.org)
  • A combination of methods was used to test the association between rare variants and pain sensitivity, and the function of the genes identified was explored using network analysis. (plos.org)
  • Using causal reasoning analysis on the genes with different patterns of SNVs by pain sensitivity status, we observed a significant enrichment of variants in genes of the angiotensin pathway (Bonferroni corrected p = 3.8×10 −4 ). (plos.org)
  • The approach of sequencing extreme exome variation in normal individuals has provided important insights into gene networks mediating pain sensitivity in humans and will be applicable to other common complex traits. (plos.org)
  • Modelling in twins, however, suggests that there are two separate predisposing genetic factors including variants that modulate sensitivity to pain, as well as those mediating anxiety and depression. (plos.org)
  • A number of approaches to pain sensitivity genetics have been adopted including the examination of rare (monogenic) syndromes of pain insensitivity (reviewed in ) and candidate genes identified from transcriptional profiling in animal models . (plos.org)
  • Whereas acute temperature-induced pain is essential to prevent or limit burn injury, pathological conditions such as inflammation or tissue injury can deregulate the thermal sensitivity of the somatosensory system, resulting in painful dysesthesias such as heat and cold hypersensitivity. (oxfordhandbooks.com)
  • In a recent Phase 3 trial with 149 participants, those receiving 30 μg of TTX twice a day for four days were more likely to report reduced pain than were those who received a placebo ( Pain Res Manag , 2017:7212713, 2017). (the-scientist.com)
  • Patients significantly overestimate the anticipated amount of pain they'll experience following surgery, which researchers say can cause unnecessary anxiety in patients, according to a study being presented at the ANESTHESIOLOGY 2017 annual meeting. (news-medical.net)
  • Itch is a major somatic sensation, along with pain, temperature, and touch, detected and relayed by the somatosensory system. (physiology.org)
  • The primary objective of the current study was to compare the efficacy of subcutaneous TTX (trade name Halneuron™) with that of placebo in patients with pain due to advanced cancer or its treatment. (hindawi.com)
  • There is an unmet medical need for treatment of cancer patients with chemotherapy induced neuropathic pain (CINP) and the proposed study will investigate the efficacy and safety of multiple dose levels of tetrodotoxin (TTX) versus placebo in moderate to severe neuropathic pain caused by chemotherapy. (clinicaltrials.gov)
  • Max dose Tetrodotoxin injectable (1 ml volume), once a day in the morning for four consecutive days and Placebo for injection (1 ml volume), once a day in the afternoon for four consecutive days. (clinicaltrials.gov)
  • The principle of infiltration analgesia is the injection of anesthetic solution very near the actual area to be treated and relying upon the solution diffusing or infiltrating to the sensory nerves so that conduction pain impulses prevented. (intelligentdental.com)
  • A single topical instillation of sConA-Lip/TD on the cornea could achieve 105 min of complete analgesia and 608 min of partial analgesia, which was significantly longer than analgesia with proparacaine, tetrodotoxin/dexmedetomidine solution or unmodified liposomes containing tetrodotoxin and dexmedetomidine. (dryeyezone.com)
  • Pharmacologically, VGSCs can be broadly classified into those that are blocked by tetrodotoxin (tetrodotoxin sensitive) and those that relatively insensitive (tetrodotoxin resistant). (asahq.org)
  • The PIIIA fraction of μ-conotoxin allows a modest pharmacologic distinction between two members of the tetrodotoxin-sensitive VGSCs as well. (asahq.org)
  • From a therapeutic perspective, what has been particularly exciting about the evidence implicating VGSCs in inflammatory and neuropathic pain, is that several of the VGSC alpha subunits shown to contribute to the injury-induced increases in afferent excitability are preferentially expressed in the peripheral nervous system in general, and nociceptive afferents in particular ( Gold and Gebhart, 2010 ). (elifesciences.org)
  • California newt and the eastern salamander) also possess tetrodotoxin in lethal quantities (3) ( Table 1 ). (cdc.gov)
  • As a result the development of subtype selective channel blockers, whilst technically challenging, is the focus of many current pain drug discovery efforts. (uclb.com)
  • But the deadly nature of this cephalopod comes from tetrodotoxin, a poison acquired from bacteria that live in various places in the body, including venom glands. (nhm.ac.uk)
  • Tetrodotoxin can act as either a poison if a predator eats the octopus, or as venom if injected through a bite. (nhm.ac.uk)
  • Significant insights into the cellular and molecular basis of cutaneous nociception have been realized from studies on conscious humans and surrogate animal models ( 15 , 16 ), although we are far from understanding the cell biology of pain perception. (jci.org)
  • Venomous centipedes may harbor a clue to the creation of a successful pain-killing compound for humans. (the-scientist.com)
  • Our results cast light on the genetic factors underlying normal pain sensation in humans and the utility of exome analyses. (plos.org)
  • Anand KJ, Coskun V, Thirvikraman KV, Nemeroff CB, Plotsky PM (1999) Long-term behavioral effects of repetitive pain in neonatal rat pups. (springer.com)
  • Pain is multidimensional, may have visceral, musculoskeletal, or neuropathic origins, and its perception is influenced by psychological factors. (pharmacytimes.com)
  • We collaborate with research groups in Europe, the United States, Korea, Japan and Australia, using transgenic mouse models, natural products and cloned genes to explore the physiology of pain perception. (ucl.ac.uk)
  • CTX, however, do not exert only venomous activity but have a lot of pharmacological properties with specific bioactivity in the treatment of neurological disorders and the associated pain perception [ 1 , 2 , 3 ]. (mdpi.com)
  • Normally, nociception (see Glossary, Sidebar 1) and the perception of pain are evoked only at pressures and temperatures extreme enough to potentially injure tissues and by toxic molecules and inflammatory mediators. (jci.org)
  • We further discuss innovations using genetic and pharmacological tools that begin to address how particular nociceptor populations contribute to the perception of specific pain qualities. (jci.org)
  • Certain other genetic defects leave people without any pain pathways in their body whatsoever, which makes their lack of pain perception easy to understand. (dana.org)
  • A de novo gain-of-function mutation in SCN11A causes loss of pain perception. (painresearchforum.org)
  • Pain perception: Is there a role for primary somatosensory cortex? (opal-libraries.org)
  • Because pain signals follow their own pathways to the brain, the family members in Pakistan are able to perceive nonpainful sensations normally. (dana.org)
  • When the sensation would become painful to most people, they continue to perceive it as normal because their pain pathways are inoperative. (dana.org)
  • Depending on the type of stimulus condition, different neural pathways are involved in chronic pain. (springer.com)
  • His research interest is in the field of axonal biology and trying to devise strategies to utilize axons as a route for drug delivery for the nervous system to treat disorders such as chronic neuropathic pain. (amrita.edu)
  • It is a tetrodotoxin-sensitive Na + channel isoform. (uniprot.org)
  • In general, a tool for selectively inhibiting the VGSC in an isoform-specific manner will lead to a deeper understanding of the functional role of VGSC isoforms in pain and other critical biologic processes. (asahq.org)