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.Pain Threshold: Amount of stimulation required before the sensation of pain is experienced.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.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.Carrageenan: 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.Pain: An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.Injections, Spinal: Introduction of therapeutic agents into the spinal region using a needle and syringe.Physical Stimulation: Act of eliciting a response from a person or organism through physical contact.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.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.Capsaicin: An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.Freund's Adjuvant: 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.Hot Temperature: Presence of warmth or heat or a temperature notably higher than an accustomed norm.Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.Spinal Cord: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.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.TRPV Cation Channels: 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.Analgesics, Opioid: Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.Touch: Sensation of making physical contact with objects, animate or inanimate. Tactile stimuli are detected by MECHANORECEPTORS in the skin and mucous membranes.Posterior Horn Cells: 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.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.Mustard Plant: 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.Sciatic Neuropathy: Disease or damage involving the SCIATIC NERVE, which divides into the PERONEAL NERVE and TIBIAL NERVE (see also PERONEAL NEUROPATHIES and TIBIAL NEUROPATHY). Clinical manifestations may include SCIATICA or pain localized to the hip, PARESIS or PARALYSIS of posterior thigh muscles and muscles innervated by the peroneal and tibial nerves, and sensory loss involving the lateral and posterior thigh, posterior and lateral leg, and sole of the foot. The sciatic nerve may be affected by trauma; ISCHEMIA; COLLAGEN DISEASES; and other conditions. (From Adams et al., Principles of Neurology, 6th ed, p1363)Hyperesthesia: Increased sensitivity to cutaneous stimulation due to a diminished threshold or an increased response to stimuli.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Inflammation: 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.Behavior, Animal: The observable response an animal makes to any situation.Nociception: Sensing of noxious mechanical, thermal or chemical stimuli by NOCICEPTORS. It is the sensory component of visceral and tissue pain (NOCICEPTIVE PAIN).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.Spinal Nerves: 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.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.Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.Visceral Pain: Pain originating from internal organs (VISCERA) associated with autonomic phenomena (PALLOR; SWEATING; NAUSEA; and VOMITING). It often becomes a REFERRED PAIN.Cyclohexanecarboxylic AcidsSciatic 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.Foot: The distal extremity of the leg in vertebrates, consisting of the tarsus (ANKLE); METATARSUS; phalanges; and the soft tissues surrounding these bones.Edema: Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.Nerve Fibers, Unmyelinated: 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.Reflex, Abdominal: Contractions of the abdominal muscles upon stimulation of the skin (superficial abdominal reflex) or tapping neighboring bony structures (deep abdominal reflex). The superficial reflex may be weak or absent, for example, after a stroke, a sign of upper (suprasegmental) motor neuron lesions. (Stedman, 25th ed & Best & Taylor's Physiological Basis of Medical Practice, 12th ed, p1073)Peripheral Nervous System Diseases: 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.Analgesia: Methods of PAIN relief that may be used with or in place of ANALGESICS.Neurons, Afferent: Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM.Sensory System Agents: 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)Hindlimb: 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)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.Visceral Afferents: The sensory fibers innervating the viscera.Receptors, Neurokinin-1: A class of cell surface receptors for TACHYKININS with a preference for SUBSTANCE P. Neurokinin-1 (NK-1) receptors have been cloned and are members of the G protein coupled receptor superfamily. They are found on many cell types including central and peripheral neurons, smooth muscle cells, acinar cells, endothelial cells, fibroblasts, and immune cells.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Receptors, N-Methyl-D-Aspartate: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.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.Injections, Intradermal: The forcing into the skin of liquid medication, nutrient, or other fluid through a hollow needle, piercing the top skin layer.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.Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Dinoprostone: The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Nerve Growth Factor: 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.Formaldehyde: 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)Trigeminal Caudal Nucleus: The caudal portion of the nucleus of the spinal trigeminal tract (TRIGEMINAL NUCLEUS, SPINAL), a nucleus involved with pain and temperature sensation.Neurokinin-1 Receptor Antagonists: Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.Medulla Oblongata: The lower portion of the BRAIN STEM. It is inferior to the PONS and anterior to the CEREBELLUM. Medulla oblongata serves as a relay station between the brain and the spinal cord, and contains centers for regulating respiratory, vasomotor, cardiac, and reflex activities.Peripheral Nerve Injuries: Injuries to the PERIPHERAL NERVES.Mononeuropathies: Disease or trauma involving a single peripheral nerve in isolation, or out of proportion to evidence of diffuse peripheral nerve dysfunction. Mononeuropathy multiplex refers to a condition characterized by multiple isolated nerve injuries. Mononeuropathies may result from a wide variety of causes, including ISCHEMIA; traumatic injury; compression; CONNECTIVE TISSUE DISEASES; CUMULATIVE TRAUMA DISORDERS; and other conditions.Amines: A group of compounds derived from ammonia by substituting organic radicals for the hydrogens. (From Grant & Hackh's Chemical Dictionary, 5th ed)Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the ENKEPHALINS, the DYNORPHINS, and the ENDORPHINS. Each of these families derives from different precursors, proenkephalin, prodynorphin, and PRO-OPIOMELANOCORTIN, respectively. There are also at least three classes of OPIOID RECEPTORS, but the peptide families do not map to the receptors in a simple way.Receptors, Opioid, mu: A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.Piperidines: A family of hexahydropyridines.Nerve Compression Syndromes: Mechanical compression of nerves or nerve roots from internal or external causes. These may result in a conduction block to nerve impulses (due to MYELIN SHEATH dysfunction) or axonal loss. The nerve and nerve sheath injuries may be caused by ISCHEMIA; INFLAMMATION; or a direct mechanical effect.Pain, Postoperative: Pain during the period after surgery.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.Lidocaine: 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.Calcitonin Gene-Related Peptide: 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.Alcoholic Neuropathy: 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)Diabetic Neuropathies: Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325)Dizocilpine Maleate: A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.Receptor, PAR-2: A G-protein-coupled, proteinase-activated receptor that is expressed in a variety of tissues including ENDOTHELIUM; LEUKOCYTES; and the GASTROINTESTINAL TRACT. The receptor is activated by TRYPSIN, which cleaves off the N-terminal peptide from the receptor. The new N-terminal peptide is a cryptic ligand for the receptor. The uncleaved receptor can also be activated by the N-terminal peptide present on the activated THROMBIN RECEPTOR and by small synthetic peptides that contain the unmasked N-terminal sequence.Electroacupuncture: A form of acupuncture with electrical impulses passing through the needles to stimulate NERVE TISSUE. It can be used for ANALGESIA; ANESTHESIA; REHABILITATION; and treatment for diseases.Myalgia: Painful sensation in the muscles.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters.Protein Kinase C-epsilon: 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.Receptors, Opioid: Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.Transient Receptor Potential Channels: 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.Acid Sensing Ion Channels: 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.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.Bradykinin: 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.Reaction Time: The time from the onset of a stimulus until a response is observed.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.Rhizotomy: Surgical interruption of a spinal or cranial nerve root. (From Dorland, 28th ed)Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.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.Anti-Inflammatory Agents, Non-Steroidal: Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Trigeminal Nerve Injuries: Traumatic injuries to the TRIGEMINAL NERVE. It may result in extreme pain, abnormal sensation in the areas the nerve innervates on face, jaw, gums and tongue and can cause difficulties with speech and chewing. It is sometimes associated with various dental treatments.Minocycline: A TETRACYCLINE analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant STAPHYLOCOCCUS infections.Hypesthesia: Absent or reduced sensitivity to cutaneous stimulation.Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines.Mice, Inbred C57BLLumbosacral Region: Region of the back including the LUMBAR VERTEBRAE, SACRUM, and nearby structures.Receptor, EphB1: An eph family receptor found primarily in the nervous system. In the embryonic BRAIN EphB1 receptor expression occurs in the mantle layer and increases with the progression of embryogenesis. In adult brain it is found in the several regions including the CEREBELLUM; CEREBRAL CORTEX; and CAUDATE NUCLEUS; and PUTAMEN.Fentanyl: A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)Anesthetics, Dissociative: Intravenous anesthetics that induce a state of sedation, immobility, amnesia, and marked analgesia. Subjects may experience a strong feeling of dissociation from the environment. The condition produced is similar to NEUROLEPTANALGESIA, but is brought about by the administration of a single drug. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed)Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Tibial Neuropathy: Disease of the TIBIAL NERVE (also referred to as the posterior tibial nerve). The most commonly associated condition is the TARSAL TUNNEL SYNDROME. However, LEG INJURIES; ISCHEMIA; and inflammatory conditions (e.g., COLLAGEN DISEASES) may also affect the nerve. Clinical features include PARALYSIS of plantar flexion, ankle inversion and toe flexion as well as loss of sensation over the sole of the foot. (From Joynt, Clinical Neurology, 1995, Ch51, p32)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.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)Receptor, Cannabinoid, CB2: A subclass of cannabinoid receptor found primarily on immune cells where it may play a role modulating release of CYTOKINES.Injections, Subcutaneous: Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.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.Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include PAIN; PARESTHESIAS; PARESIS; or HYPESTHESIA.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Tolmetin: A non-steroidal anti-inflammatory agent (ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL) similar in mode of action to INDOMETHACIN.