Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Capsaicin has been used extensively as an experimental tool and in traditional and proprietary topical medications for acute soft tissue injuries. More recently it has been prescribed for several chronic pain conditions where it is usually administered topically for periods of several weeks. Here we have studied the consequences of this mode of application in the rat. Capsaicin cream (0.075% or 0.75%), or a vehicle cream, was applied twice daily to the hind paws of rats for a continuous period of 10 weeks. The hind paws treated with 0.75% capsaicin (but not 0.075%) because transiently hyperalgesic, but there were no signs of discomfort or distress associated with the treatment. After 10 weeks of capsaicin application, the ability of C fibres to produce neurogenic extravasation was markedly reduced. After 4 weeks of recovery this ability returned to normal in 0.075% capsaicin-treated animals, but remained impaired in the 0.75% group. This latter group showed a partial recovery 12 weeks after the end of treatment. The levels of substance P and CGRP in the sural nerve supplying the treated skin area were unchanged after both the 0.075% and 0.75% capsaicin treatments. The results suggest that the topical application of capsaicin at low concentration produces a reversible impairment of the terminals of C fibres in the skin without greatly exciting those fibres and without affecting the properties of cell soma. The number of afferent neurones in the L5 dorsal root ganglion projecting through the sural nerve was unchanged after 0.75% capsaicin treatment, suggesting that the topical capsaicin treatment does not produce any cell death in the adult animal.
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PMID:The consequences of long-term topical capsaicin application in the rat. 205

The tachykinins eledoisin, substance P and kassinin were administered by pulse intracerebroventricular (ICV) injections to cats made thirsty by ICV angiotensin II, 100 ng per cat. Eledoisin, 100 ng per cat, produced an inhibition of drinking which was larger (56.0 vs. 45.2%) and lasted longer than that evoked by 400 ng per cat of substance P. Kassinin, 100 ng per cat, did not evoke any effect at all. The treatment with these peptides neither produced signs of discomfort nor induced any other behavioural alteration. The results of present experiments suggest that the antidipsogenic effect of tachykinins is a phenomenon of general interest among mammals.
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PMID:Inhibitory effect of intracranial injections of tachykinins on angiotensin-induced drinking in the cat. 246 87

Orthodontic treatment typically involves intermittent periods of patient discomfort caused by forces on the teeth and adjacent tissues. This sensation of discomfort presumably is caused by the action of neuropeptides in the peripheral and central nervous systems. The effects of orthodontic force on the concentrations of two endogenous neuropeptides, methionine enkephalin (ME) and substance P (SP), measured as immunoreactive-methionine enkephalin (ir-ME) and immunoreactive-substance P (ir-SP), in human tooth pulp were evaluated in 20 patients from whom premolars were extracted before orthodontic treatment. The teeth from nine controls were not subjected to a force, whereas the 11 experimental patients had force applied to their maxillary premolars either by a transpalatal spring ligature or, in one case, by a headgear. The ligature applied a force within the range of 120 to 245 gm; the headgear applied 600 gm. Reversed-phase high-performance liquid chromatography (RP-HPLC) was used to purify the neuropeptides in the pulp homogenate, and radioimmunoassay (RIA) was used to quantify ir-ME and ir-SP in their appropriate HPLC fractions. (1) Females subjected to orthodontic force had significantly greater ir-ME concentrations than males. (2) The ir-SP concentration decreased significantly from the first to the third tooth extracted, then increased from the third to the fourth tooth. (3) Ir-SP and ir-ME concentrations are positively intercorrelated. The association was highest in the first tooth extracted from controls; surgical extraction decreased the correlation, although it continued to be positive. (4) The concentrations of ir-ME and ir-SP each correlated negatively with the magnitude of the orthodontic force and that correlation was enhanced when the value of the force was log-transformed.
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PMID:Effects of orthodontic force on methionine enkephalin and substance P concentrations in human pulpal tissue. 247 5

Complications of the gastrointestinal tract in patients with diabetes mellitus can cause marked discomfort and may modify the ability of the patient to maintain normal glucostasis. In an attempt to elucidate some of the factors causing gastrointestinal dysfunction in experimental diabetes we examined the responses of jejunal smooth muscle in streptozotocin-induced diabetes in rats to some of the neurotransmitters and autocoids found in the enteric nervous system. Jejunal tissues from 4- to 5-week diabetic rats were examined for their responses to neurokinin (NK) A, NKB, substance P (SP), bradykinin, neurotensin, bethanechol, isoproterenol and phenylephrine. The affinities for all these agonists, except for SP which increased slightly with diabetes, were the same in both control and diabetic tissues. NKA was the most potent neurokinin and elicited the largest contractile responses from jejunal tissues of both control and diabetic animals. The contractile response to NKA, but not that to NKB or SP, was increased in the jejunum from diabetic animals. Part of this increased responsiveness was antagonized by atropine. The contractile effects of the cholinergic agonist, bethanechol, were not altered by the diabetic state. Decreased relaxation responses in the jejunum from diabetic animals were observed for bradykinin, neurotensin and isoproterenol, but not for phenylephrine. These results suggest that the myogenic actions of several agonists are modified in experimental diabetes.
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PMID:Modified smooth muscle responses of jejunum in streptozotocin-diabetic rats. 290 44

Idiopathic vulvodynia is vulvar discomfort in which a diagnosis has not yet been established. As in other idiopathic pain syndromes, the involvement of primary afferent fibers (PAFs) has been postulated as playing a role in the pathogenesis and maintenance of idiopathic vulvodynia. Capsaicin induces the release of substance P (SP) by PAFs, producing vasodilation and increasing vascular permeability (neurogenic inflammation). Likewise, it has been shown that acid solutions can stimulate PAFs with the release of SP. To evaluate the pain threshold in women with idiopathic vulvodynia, 10 patients with vulvar pain but without significant vulvar physical changes and 10 asymptomatic controls received topically applied acetic acid solutions with increasing hydrogenionic concentrations (pH 3, 2.5, 2, 1.5, 1.2). Results related to pain threshold and pain time monitoring and intensity were analyzed with Fisher's exact and Wilcoxon's tests, respectively. Our data suggest that in idiopathic vulvodynia the pain threshold for acid solutions is decreased, probably in relation to increased sensitivity of PAFs involved in the transduction of painful signals.
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PMID:Idiopathic vulvodynia. Clinical evaluation of the pain threshold with acetic acid solutions. 760 71

Traumatic injury to the peripheral nerves often results in persistent discomfort. Substance P has been implicated as a mediator of pain, and depletion of this neurotransmitter has been shown to reduce pain. Subjects suffering from traumatic dysesthesia of the trigeminal nerve were treated with capsaicin, a substance P depleter with significant long-term effects. This form of therapy may be used individually or in combination with other pharmacologic interventions in the treatment of traumatic trigeminal dysesthesia.
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PMID:Traumatic dysesthesia of the trigeminal nerve. 767 Apr 27

Ten healthy volunteers (five men and five women, mean age 30 years 3 months), with no nasal contact points, had pressure, adrenaline (1 : 1000), substance P (10 and 80 nmol/mL) and placebo topically applied to their nasal mucosa. Areas stimulated were the nasal floor, septum and lateral wall as well as the inferior and middle turbinates in both nasal cavities. The application of stimuli was randomized and single-blinded. A numerical score of the subjective severity of pain was used to assess outcome. Pressure caused variable local nasal discomfort limited by the duration of application and the site of pressure. Substance P caused variable nasal itching and sneezing. None of the stimuli caused referred pain to the face. The results question the role of mucosal contact points in facial pain.
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PMID:Does stimulation of nasal mucosa cause referred pain to the face? 1167 53

An intricate surveillance network consisting of enteroendocrine cells, immune cells and sensory nerve fibres monitors the luminal and interstitial environment in the alimentary canal. Functional bowel disorders are characterized by persistent alterations in digestive regulation and gastrointestinal discomfort and pain. Visceral hyperalgesia may arise from an exaggerated sensitivity of peripheral afferent nerve fibres and/or a distorted processing and representation of gut signals in the brain. Novel strategies to treat these sensory bowel disorders are therefore targeted at primary afferent nerve fibres. These neurons express a number of molecular traits including transmitters, receptors and ion channels that are specific to them and whose number and/or behaviour may be altered in chronic visceral pain. The targets under consideration comprise vanilloid receptor ion channels, acid-sensing ion channels, sensory neuron-specific Na(+) channels, P2X(3) purinoceptors, 5-hydroxytryptamine (5-HT), 5-HT(3) and 5-HT(4) receptors, cholecystokinin CCK(1) receptors, bradykinin and prostaglandin receptors, glutamate receptors, tachykinin and calcitonin gene-related peptide receptors as well as peripheral opioid and cannabinoid receptors. The utility of sensory neuron-targeting drugs in functional bowel disorders will critically depend on the compounds' selectivity of action for afferent versus enteric or central neurons.
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PMID:Gastrointestinal afferents as targets of novel drugs for the treatment of functional bowel disorders and visceral pain. 1169 40

Functional dyspepsia is a clinical syndrome defined by chronic or recurrent pain or discomfort in the upper abdomen of unknown origin. Although generally accepted, investigators differently interpret this definition and clinical trials are often biased by inhomogeneous inclusion criteria. The poorly defined multifactorial pathogenesis of dyspeptic symptoms has hampered efforts to develop effective treatments. A general agreement exists on the irrelevant role played by Helicobacter pylori in the pathophysiology of functional dyspepsia. Gastric acid secretion is within normal limits in patients with functional dyspepsia but acid related symptoms may arise in a subgroup of them. Proton pump inhibitors appear to be effective in this subset of patients with dyspepsia. Non-painful dyspeptic symptoms are suggestive of underlying gastrointestinal motor disorders and such abnormalities can be demonstrated in a substantial proportion of patients. Postprandial fullness and vomiting have been associated with delayed gastric emptying of solids, and early satiety and weight loss to postcibal impaired accommodation of the gastric fundus. Prokinetics have been shown to exert beneficial effects, at least in some patients with dyspepsia. In contrast, drugs enhancing gastric fundus relaxation have been reported to improve symptoms, although conflicting results have also been published. An overdistended antrum may also generate symptoms, but its potential pathogenetic role and the effects of drugs on this abnormality have never been investigated formally. Visceral hypersensitivity plays a role in some dyspeptic patients and this abnormality is also a potential target for treatment. Both chemo- and mechanoreceptors can trigger hyperalgesic responses. Psychosocial abnormalities have been consistently found in functional digestive syndromes, including dyspepsia. Although useful in patients with irritable bowel syndromes (IBS), antidepressants have been only marginally explored in functional dyspepsia. Among the new potentially useful agents for the treatment of functional dyspepsia, serotonin 5-HT(4) receptor agonists have been shown to exert a prokinetic effect. Unlike motilides, 5-HT(4) receptor agonists do not appear to increase the gastric fundus tone and this may contribute to improve symptoms. 5-HT(3) receptor antagonists have been investigated mainly in the IBS and the few studies performed in functional dyspepsia have provided conflicting results. Also, kappa-opioid receptor agonists might be useful for functional digestive syndromes because of their antinociceptive effects, but available results in functional dyspepsia are scanty and inconclusive. Other receptors that represent potential clinical targets for antagonists include purinoceptors (i. e., P2X2/3 receptors), NMDA receptors (NR2B subtype), protease-activated receptor-2, the vanilloid receptor-1, tachykinin receptors (NK(1)/NK(2)) and cholecystokinin (CCK)(1) receptors.
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PMID:New developments in the treatment of functional dyspepsia. 1267 73

Healed partial thickness wounds including burns and donor sites cause hypertrophic scar formation and patient discomfort. For many patients with hypertrophic scars, pruritus is the most distressing symptom, which leads to wound excoriation and chronic wound formation. In spite of the clinical significance of abnormal innervation in scars, the nervous system has been largely ignored in the pathophysiology of hypertrophic scars. Evidence that neuropeptides contribute to inflammatory responses to injury include inflammatory cell chemotaxis, cytokine and growth factor production. The neuropeptide substance P, which is released from nerve endings after injury, induces inflammation and mediates angiogenesis, keratinocyte proliferation, and fibrogenesis. Substance P activity is tightly regulated by neutral endopeptidase (NEP), a membrane bound metallopeptidase that degrades substance P at the cell membrane. Altered substance P levels may contribute to impaired cutaneous healing responses associated with diabetes mellitus or hypertrophic scar formation. Topical application of exogenous substance P or an NEP inhibitor enhances wound closure kinetics in diabetic murine wounds suggesting that diabetic wounds have insufficient substance P levels to promote a neuroinflammatory response necessary for normal wound repair. Conversely, increased nerve numbers and neuropeptide levels with reduced NEP levels in human and porcine hypertrophic scar samples suggest that excessive neuropeptide activity induces exuberant inflammation in hypertrophic scars. Given these observations about the role of neuropeptides in cutaneous repair, neuronal modulation of repair processes at two extremes of abnormal wound healing, chronic non-healing ulcers in type II diabetes mellitus and hypertrophic scars in deep partial thickness wounds, may provide therapeutic targets.
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PMID:Making sense of hypertrophic scar: a role for nerves. 1772 64


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