Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Capsaicin selectively excites C-polymodal nociceptors in mammalian skin. In the rat, the only species so far studied in detail, a long-term desensitization of a subpopulation of C-polymodal nociceptors occurs after the initial excitation. After nerve treatment, permanent loss of some C-polymodal nociceptors is found in the rat. It is argued that capsaicin must act primarily on C fibres involved in signalling about pain and not itch, although there may be overlap between the C afferents involved in these two nociceptive sensations. The possibility is raised that C mechanoreceptors, with their good histamine sensitivity, are also involved in itch.
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PMID:Capsaicin: actions on C fibre afferents that may be involved in itch. 157 83

Topical capsaicin has been introduced in the U.S. and Canada as a cream indicated for temporary relief of neuralgia following episodes of herpes zoster infections and in the treatment of diabetic neuropathy. Although capsaicin is clinically used as an external analgesic for temporary relief of neuralgia, it has also been widely used as a research tool to study peripheral pain. Capsaicin apparently works to release substance P from sensory nerve fibers and after repeated applications, depletes neurons of substance P. Clinical investigations of topical capsaicin include trials in chronic pain syndromes such as postherpetic neuralgia, postmastectomy neuroma, reflex sympathetic dystrophy syndrome, diabetic neuropathy, rheumatoid arthritis, psoriasis, hemodialysis-associated itching, and vulvar vestibulitis. In addition, therapeutic benefits of capsaicin cream on apocrine chromhidrosis have been described. Further clinical studies are warranted in several of these conditions to establish the efficacy of topical capsaicin. Serious or unexpected adverse reactions from clinical use have not been reported to date. Considering the paucity of safe and effective treatments for the conditions mentioned above, capsaicin cream appears to warrant further clinical investigations to establish its efficacy in a variety of chronic pain syndromes.
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PMID:Topical capsaicin in dermatologic and peripheral pain disorders. 165 16

Cutaneous sensibility and neurogenic vasodilatation (flare) were measured before, during and after long-term topical application of capsaicin in humans. Each subject applied a vehicle cream containing 0.075% capsaicin (Axsain, GalenPharma Inc.) to a 4 cm2 area of skin on one volar forearm and vehicle alone to an identical treatment area on the other forearm, according to a double-blind procedure. Each substance was applied 4 times/day for 6 weeks. Psychophysical measurements of sensory detection thresholds, magnitude of suprathreshold heat pain, magnitude and duration of histamine-induced itch and flare area were obtained before, at 1, 3 and 7 days after the first application, and once a week thereafter for a total of 8 weeks. Capsaicin produced mild burning in all subjects which diminished in magnitude and duration over several weeks. Capsaicin significantly altered detection thresholds for heat pain and the magnitude of pain produced by suprathreshold painful stimuli. Mean detection threshold for heat pain was lowered 1.6 degrees C following 1 day of capsaicin application but subsequently increased to become elevated 3.5 degrees C after 6 weeks of application. In addition, mean magnitude of suprathreshold heat pain diminished progressively after 1 week. Heat pain thresholds returned to or near pretreatment values within 2 weeks after discontinuing application. Detection thresholds for touch, cold sensation and pain induced by low temperature and by mechanical stimulation were not altered by capsaicin. Similarly, capsaicin did not alter the magnitude or duration of itch produced by intradermal injection of 1 microgram histamine. However, the area of flare produced by histamine was significantly reduced in capsaicin-treated skin. These studies demonstrate that prolonged application of capsaicin at low concentration selectively diminishes sensations of heat pain and neurogenic vasodilatation, presumably via desensitization of heat-sensitive nociceptors. It is also shown that the decrease in heat pain is temporary and is maintained with repeated capsaicin application. There appears to be a therapeutic role for capsaicin in cutaneous painful syndromes mediated, at least in part, by activity of heat-sensitive nociceptors.
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PMID:Early and late effects of prolonged topical capsaicin on cutaneous sensibility and neurogenic vasodilatation in humans. 166 7

The effects of topical treatment with capsaicin or mustard oil on histamine-induced pruritus, wheal formation and flare response were studied in the human skin. Capsaicin pretreatment resulted in a reversible marked reduction or abolition of the axon reflex flare, but did not influence whealing. Itching was also strongly diminished or even abolished, provided that the flare response was completely blocked. The onset of itching was significantly promoted by pretreatment of the skin with mustard oil, inducing axon reflex vasodilatation. It is concluded that, in addition to the axon reflex flare, capsaicin-sensitive peptide-containing primary afferent neurones are also intimately involved in the mediation of the sensation of itching.
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PMID:Capsaicin prevents histamine-induced itching. 372 47

Apart from adrenergic and cholinergic neurones, peptidergic neurones are involved in the autonomic control of nasal mucosa. Their transmitter substances are peptides, so-called "neuropeptides". It is assumed that they are released from peptidergic neurones in the nasal mucosa after irritation of receptors by unspecific stimuli, and are responsible for the symptoms of hyperreactive rhinopathy. Repeated topical application of Capsaicin (8-methyl-N-vanillyl-6-nonenamide) leads to a selective degeneration of peptidergic neurones and desensitisation of its receptors in the nasal mucosa. 123 patients who were suffering from hyperreactive rhinopathy were treated in a prospective study by repeated topical applications of capsaicin solutions in increasing concentrations. A symptom score demonstrated an improvement of the predominating symptoms (nasal congestion, hypersecretion, sneezing) by 62% to 72%. A reduction of unpleasant side effects following application (epiphora, itching, sneezing, mucosal oedema) indicating a desensitising effect could be documented by a symptom score and by active anterior rhinomanometry. Immunohistochemical investigations of nasal mucosa biopsies revealed no reduction of peptidergic neurones within the nasal mucosa, so that a blockage of receptors seems to be responsible for the positive effects. The treatment of hyperreactive rhinopathy with capsaicin or related substances seems to be a promising new way in the treatment of hyperreactive rhinopathy. Further investigations have to prove the site of effect and mechanism of activity of the substance, such as the best modality of application.
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PMID:[Treatment of nonspecific hyper-reflectory rhinopathy (vasomotor rhinitis) with capsaicin]. 760 68

Nodular prurigo (NP) is a chronic skin disease causing severe itch of unknown origin in restricted skin areas surrounded by healthy skin areas. In the present investigation we studied cutaneous sensibility in five NP-patients and in five control subjects. Pain thresholds were determined with short argon laser pulses using two different sizes of stimulus surface (diameters 2 and 4 mm), tactile threshold with calibrated monofilaments and skin blood flow with a laser Doppler flowmeter. We also studied the effect of prolonged capsaicin treatment which should predominantly impair the function of nociceptive C-fibers. In both the itching and healthy skin areas the pain thresholds were lower in NP-patients than in healthy control subjects. Before capsaicin, an increase in stimulus area produced an equal decrease in pain threshold in all subjects. Following prolonged capsaicin treatment the pain threshold obtained with a large but not a small stimulus surface was elevated to control levels in NP-patients. Tactile thresholds in NP-patients were lower than in control subjects, and this abnormality was reversed by capsaicin. The basal skin blood flow level was more labile (fluctuating) in itching skin areas than in healthy skin areas of NP-patients. Capsaicin reduced blood flow fluctuation in the itching area. A lowered pain threshold not only in the itching area but also in the healthy skin area of NP-patients suggests that central convergence of itch and pain may contribute to increased pain sensitivity in chronic itch. Capsaicin-reversible abnormal fluctuation of the blood flow in the itching skin area might be explained by abnormal spontaneous activity of nociceptive peripheral nerve fibers and a consequent release of vasoactive agents from their terminals (axon reflex). The decreased tactile threshold and the elevation of it by capsaicin indicates that also the mechanisms underlying tactile sensibility are changed in chronic itch patients.
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PMID:Altered skin sensitivity in chronic itch: role of peripheral and central mechanisms. 921 42

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is thought to produce analgesic and possibly also antipruritic effects when applied topically. Capsaicin 0.05% was applied three times daily over a 5-day period to the same infrascapular region. The effects of the pretreatment upon the pruritogenic and wheal and flare reactions to subsequent histamine iontophoresis (20 mC) were evaluated on the following day. The antipruritic effects of the pretreatment were compared with the effects of placebo pretreatment and no pretreatment. Wheal and flare areas were evaluated planimetrically. Itch or pain were rated every minute over a 24-min period. The areas of alloknesis, i.e. the induction of perifocal itch sensation by usually nonitching (e.g. mechanical) stimuli, were also evaluated. In control subjects, but not in atopic eczema (AE) patients, capsaicin pretreatment significantly reduced the flare area. Compared with control subjects, AE patients showed a lack of alloknesis or significantly smaller areas of alloknesis in pretreated and nonpretreated skin. In control subjects, capsaicin pretreatment significantly reduced itch sensations compared with nonpretreated skin, whereas in AE patients no differences were seen. Itch sensations in capsaicin-pretreated skin were significantly lower in control subjects than in AE patients. We conclude that capsaicin does effectively suppress histamine-induced itching in healthy skin but has less effect in AE. The diminished itch sensations and the absence of alloknesis in atopic individuals indicate that histamine is not the key factor in itching in AE.
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PMID:Effect of topical capsaicin on the cutaneous reactions and itching to histamine in atopic eczema compared to healthy skin. 970 61

Capsaicin, which has been studied extensively as a treatment for itch and several chronic pain disorders, induces burning during the first week of therapy, causing a substantial percentage of patients to discontinue treatment prematurely. We examined whether pre-treatment with the topical anesthetic EMLA reduces the burning sensation induced by capsaicin and alters capsaicin effects on thermal sensation and pain thresholds. Healthy adult volunteers participated in the single-blind, 6-day study. After baseline measurement of warmth, cold pain and heat pain thresholds with a computerized thermal sensory analyzer, subjects applied EMLA thrice daily on one forearm and vehicle placebo on the other forearm, 60 min before applying capsaicin 0.075% on both forearms. Subjects rated burning sensations 3 times a day throughout the study. After 1 and 5 days of thrice daily application of EMLA or vehicle followed by capsaicin, thermal sensory testing was repeated. Subjects rated burning sensations to the significantly less on the EMLA pre-treated forearm compared with the placebo pre-treated forearm during all 5 days of treatment (p < 0.01). Capsaicin with and without EMLA produced significant heat pain hyperalgesia and cold pain hypoalgesia after 1 day of treatment. After 5 days of treatment, heat pain hyperalgesia persisted on both forearms; however, it was significantly less on the EMLA-treated forearm vs the vehicle-treated site (p < 0.03). Cold pain hypoalgesia persisted in both forearms. The warmth sensation threshold was significantly higher on the EMLA-pre-treated forearm after 1 and 5 days of treatment. In conclusion, pre-treatment with EMLA significantly reduced the burning sensation from capsaicin and attenuated heat hyperalgesia during treatment.
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PMID:Effect of EMLA pre-treatment on capsaicin-induced burning and hyperalgesia. 1022 29

Capsaicin applied topically to human skin produces itching, pricking and burning sensations due to excitation of nociceptors. With repeated application, these positive sensory responses are followed by a prolonged period of hypalgesia that is usually referred to as desensitization, or nociceptor inactivation. Consequently, capsaicin has been recommended as a treatment for a variety of painful syndromes. The precise mechanisms that account for nociceptor desensitization and hypalgesia are unclear. The present study was performed to determine if morphological changes of intracutaneous nerve fibers contribute to desensitization and hypalgesia. Capsaicin (0.075%) was applied topically to the volar forearm four times daily for 3 weeks. At various time intervals tactile, cold, mechanical and heat pain sensations were assessed in the treated and in contralateral untreated areas. Skin blisters and skin biopsies were collected and immunostained for protein gene product (PGP) 9.5 to assess the morphology of cutaneous nerves and to quantify the number of epidermal nerve fibers (ENFs). Capsaicin resulted in reduced sensitivity to all cutaneous stimuli, particularly to noxious heat and mechanical stimuli. This hypalgesia was accompanied by degeneration of epidermal nerve fibers as evidenced by loss of PGP 9.5 immunoreactivity. As early as 3 days following capsaicin application, there was a 74% decrease in the number of nerve fibers in blister specimens. After 3 weeks of capsaicin treatment, the reduction was 79% in blisters and 82% in biopsies. Discontinuation of capsaicin was followed by reinnervation of the epidermis over a 6-week period with a return of all sensations, except cold, to normal levels. We conclude that degeneration of epidermal nerve fibers contributes to the analgesia accredited to capsaicin. Furthermore, our data demonstrate that ENFs contribute to the painful sensations evoked by noxious thermal and mechanical stimuli.
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PMID:Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation. 1035 1

Vanilloid receptor subtype 1 (VR1), a capsaicin receptor, is expressed in primary sensory neurons and vagal nerves. Heat and protons as well as capsaicin activate VR1 to induce the influx of cations, particularly Ca2+ and Na+ ions. Characteristic effects of capsaicin are the induction of a burning sensation after acute administration and the desensitization of sensory neurons after large doses and prolonged administration. The latter feature made capsaicin cream applicable for the treatment of chronic pain and pruritus. Capsaicin alters several visceral functions, which may be mediated by action on vagal nerves and central neurons. Capsaicin affects thermoregulation after intra-hypothalamic injection and releases glutamate from the hypothalamus and cerebral cortex slices, while VR1-like immunoreactivity is not apparent in these regions. These findings taken together suggest the existence of other subtypes of vanilloid receptors in the brain.
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PMID:Peripheral and central actions of capsaicin and VR1 receptor. 1049 26


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