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)

Substance P is a neuropeptide (contained in/and released from the A delta and C nerve fibers of the skin), which provokes erythema, edema, and pruritus after intradermal injection. Local pretreatment with capsaicin produces decreased substance P-dependent erythema, with edema similar to that observed before pretreatment with capsaicin. We injected histamine and in a parallel experiment, substance P in five volunteers before and after local treatment with capsaicin, with 48/80, after 5 days of hydroxyzine. The injection of SP provoked erythema centered by a wheal. After treatment with 48/80, SP provoked increased erythema and a wheal. After hydroxyzine treatment, the injection of histamine produced no erythema or edema in four of the five subjects, while SP provoked erythema in all five subjects and edema similar to that observed before treatment with hydroxyzine. These data support the hypothesis that substance P provokes erythema and edema both with histamine-dependent and histamine-independent pathways.
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PMID:Substance P provokes cutaneous erythema and edema through a histamine-independent pathway. 137 8

Skin reactions and itch or burning pain sensations following intradermal injection of the neuropeptide substance P and topical application of the substance P releasing agent mustard oil were studied in 20 atopic dermatitis patients and 20 healthy controls. Changes in skin blood flow were measured with a Laser Doppler flowmeter. Areas of wheal and flare reactions were evaluated planimetrically. Simultaneous with Laser Doppler flowmeter measurements, subjective itch and burning pain ratings were verbally reported on a category partitioning scale at 10-second intervals. Substance P evoked dose-dependent wheal, flare, and itch reactions in both patients and controls. However, substance P doses of 10(-9) -10(-11) mol elicited smaller flares in patients than in the controls whereas the wheal sizes were similar in both groups. Substance P-induced itch ratings were lower in patients at a dose of 10(-10) mol, and the onset of itching was delayed at all substance P levels applied. Mustard oil elicited similar neurogenic inflammatory reactions in both groups, although pain sensations were significantly delayed in atopic dermatitis patients at two mustard oil concentrations, which is further indication of a desensitization of afferent nerve endings contributing to the neurogenic inflammatory reactions in the skin of these patients.
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PMID:Reactions to intradermally injected substance P and topically applied mustard oil in atopic dermatitis patients. 171 19

Pruritus is a significant problem for many patients undergoing long-term hemodialysis. Topical capsaicin depletes and prevents the reaccumulation of substance P in peripheral sensory neurons. Substance P functions in the transmission of pain and probably itch sensations. An open-label, uncontrolled trial and a double-blind, vehicle-controlled trial were conducted to evaluate the efficacy and safety of capsaicin 0.025% cream in the treatment of localized areas of pruritus in patients undergoing long-term hemodialysis. Eight of nine evaluable patients in the open-label trial reported marked relief or complete resolution of itching during the study period, and two of five evaluable patients in the double-blind trial reported complete resolution of itching in the capsaicin-treated arm with no or minimal improvement in the vehicle-treated arm. Twelve patients in the open-label trial and two in the double-blind trial were unevaluable. No serious treatment-related adverse reactions occurred.
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PMID:Topical capsaicin for treatment of hemodialysis-related pruritus. 173 43

To study the nasal response to serotonin, 14 asymptomatic hay fever patients received intranasal serotonin in increasing doses. Itching and the number of sneezes were noted, and the amount of secretion was measured and assayed for substance P. Nasal airway resistance was recorded by active posterior rhinomanometry. Serotonin induced a dose-dependent increase in nasal itching, number of sneezes and secretion. Substance P was found in 41 of 42 secretions. The median concentration was 10.3 pmol/l (range 0-28.9), and increased parallel to increasing doses of serotonin (P less than 0.001).
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PMID:Nasal challenge with serotonin in asymptomatic hay fever patients. 244 28

The etiology of atopic pruritus is unclear and seems mostly histamine-independent. In order to investigate non-mast cells as possible sources of pruritogenic agents, peripheral blood mononuclear cells from 12 atopic eczema patients and 12 controls were incubated in vitro for 24 h with phytohemagglutinin or concanavalin A (both at 10 micrograms/ml) or with medium alone, and each subject was tested with his own cell supernatants and lysates by prick testing and by application on tape-stripped skin. Histamine (0.1%) and substance P (500 microM) were tested in comparison, and reactions were observed for up to 24 h. Cell supernatants were also analysed for their contents of several cytokines. Lymphocyte cell extracts or supernatants failed to cause symptoms in controls but induced whealing in 6 and itching in 3 patients on prick testing within 5 min, lasting for 30 min in 2 patients and persisting for 6 h in 1 patient. Histamine caused itching in all controls and in 7 patients within 5 min on prick testing, with decreasing reactivity at later times. Substance P yielded results with lower values. With all three types of test reagents, fewer subjects reacted on tape stripped skin. High levels of interleukins 2 and 6, low levels of interferon and no detectable levels of interleukin 4 and tumour necrosis factor were measured in stimulated cell supernatants and extracts, with even lower levels in subjects exhibiting skin reactivity. These findings thus provide evidence that as yet unidentified mononuclear cell products may be involved in whealing and itching associated with atopic eczema.
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PMID:Pruritogenic effects of mitogen-stimulated peripheral blood mononuclear cells in atopic eczema. 865 Oct 16

Pruritus is a significant symptom among patients receiving hemodialysis. However, its underlying mechanisms remain obscure. Substance P, a neuropeptide, has been implicated in the mediation of pain and some itch sensations. Local application of capsaicin depletes the peripheral neurons of substance P and may block the conduction of pain or pruritus. This study aims to assess the efficacy and safety of capsaicin 0.025% cream in the treatment of hemodialysis-related pruritus and to further explore the underlying pathomechanism. Nineteen hemodialysis patients with idiopathic, moderate (n = 5) to severe (n = 14) pruritus were examined in a double-blind, placebo-controlled, crossover study and 17 of them completed the study. Topical agent of capsaicin or placebo base cream was applied to localized areas of pruritus 4 times a day. The severity of pruritus and treatment-related side effects (cutaneous burning/stinging sensations, dryness, or erythema) were evaluated weekly. The results showed (1) that 14 of 17 patients reported marked relief and 5 of these 14 patients had complete remission of pruritus during capsaicin treatment (Wilcoxon signed-ranks test, 2p < 0.001); (2) capsaicin was significantly more effective than placebo (Mann-Whitney rank sum test, 2p < 0.001) and a prolonged antipruritic effect was observed 8 weeks posttreatment; (3) no serious side effects were noted during the study and (4) there were no significant changes in serum concentrations of albumin, calcium, phosphorus, alkaline phosphatase, or intact parathyroid hormone during the treatment with either capsaicin or placebo. In summary, the present study indicates indirectly that idiopathic pruritus in some patients on maintenance hemodialysis may be transmitted by substance P from the peripheral sensory neurons to the central nervous system. Topical capsaicin with the unique pharmacological effect is demonstrated to markedly improve the pruritus of these patients.
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PMID:Hemodialysis-related pruritus: a double-blind, placebo-controlled, crossover study of capsaicin 0.025% cream. 873 Apr 31

There is increasing evidence that neuropeptides may be involved in the pathogenesis of atopic dermatitis (AD). This study examines whether neuropeptide distribution in the skin of patients with AD differs from normal controls. The distribution and density of several neuropeptides were examined in lesional and non-lesional skin of AD patients (n = 5) and in normal controls (n = 4) using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Staining with the general neuronal marker protein gene product 9 x 5 showed a subepidermal network of nerves with fibres penetrating the epidermis, and nerves around blood vessels, sweat glands and hair follicles. Image analysis of nerves around sweat glands showed a significantly higher nerve density in non-lesional compared with both normal controls and lesional skin (P < 0.05); lesional compared with control skin showed no significant difference. In the epidermis the density of nerves was not significantly greater in non-lesional compared with lesional skin and controls. Calcitonin gene-related peptide immunoreactivity was similar in all subjects except in three of the AD patients, where more nerves appeared to penetrate the epidermis. Substance P immunoreactivity in the papillary dermis was seen in all AD patients but no controls. Vasoactive intestinal polypeptide and neuropeptide Y staining were similar in all groups. Acetylcholinesterase-positive nerves were found around sweat glands in all subjects, the staining being greatest in non-lesional and least in lesional skin. Occasional nerves were seen in the papillary dermis in lesional skin of two out of the four patients. We have demonstrated quantitative differences in nerve growth in clinically normal skin of AD patients, and altered cutaneous neuropeptide expression in these patients which may contribute to the pathogenesis of AD. The cause of atopic dermatitis (AD) has not been fully established but it is believed that there is a complex interaction between genetic susceptibility, precipitating environmental factors and disordered immune responsiveness. There is increasing evidence that neuropeptides may be involved in the pathogenesis of AD. Exacerbations of the disease can be provoked by stress, scratching and sweating which may be the result of neurogenic inflammation. One of the first features of an exacerbation is flushing of the affected skin and pruritus. Several neuropeptides that have been identified in human skin are potent inducers of vasodilation and may induce pruritus. Substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) all cause vasodilation when injected intradermally, and SP and CGRP have been shown to be mediators of the weal and flare reaction. Spantide, a competitive antagonist of SP, has been shown to inhibit immediate and delayed-type hypersensitivity reactions. Part of these responses may be due to release of histamine and indeed elevated concentrations of histamine have been found in vivo in the skin and plasma of patients with AD. In this study the distribution and density of several neuropeptides were examined in lesional and nonlesional skin of AD patients and in normal controls using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Because many afferent fibres do not express CGRP or SP, the general neuronal marker protein gene product (PGP 9 x 5) was used to assess the overall nerve supply to the skin.
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PMID:Neuropeptides in the skin of patients with atopic dermatitis. 885 37

Knowledge of biochemical and molecular events during burn wound healing may optimize treatment of patients with thermal injuries. Substance P (SP), a neuropeptide present in C fibers of the skin, has been implicated as a mediator of inflammation and wound healing. This neuropeptide induces vasodilitation and vascular permeability by stimulating endothelial cells to round up, vascular smooth cells to relax, and mast cells to release histamine. SP also induces cytokine release by macrophages and neutrophils. Because many of the functions of SP seemed relevant to wound repair in burns, we used immunocytochemistry to characterize SP+ nerve fibers in healing human burn wounds. Deep partial-thickness burns collected from 20 patients at the time of excision and grafting were formalin fixed, paraffin-embedded, sectioned, and labeled with a monoclonal antibody to SP with use of an immunoperoxidase technique. Our tissue samples included normal skin and 20 specimens from postburn days 2 through 49. In normal adult skin, SP+ nerve fibers surrounded vessels throughout the skin and extended from the papillary dermis into the epidermis. SP+ fibers were absent in early wound beds. SP immunostaining did occur in the advancing epidermis, endothelial cells, and mast cells. SP+ fibers could be identified in the deep dermis and subjacent to the advancing epithelium before the wound beds. Maximum numbers of SP+ fibers were present subjacent to the advancing epithelium at 2 weeks after burn injury. After 4 weeks, the distribution of SP+ fibers in reepithelialized areas was similar to that of normal skin. Our data corroborate published reports of SP+ fiber regeneration in guinea pig burns and correlates with clinical observations of pain and pruritus in patients with thermal injuries. The absence of SP+ fibers in the early wounds with SP immunostaining in the epidermis and extracellular matrix suggests that SP may be released from injured nerves and supports neurogenic mediation of inflammation and vasodilitation in early wound repair. Repopulation of the wound beds with SP+ fibers appeared to follow neovascularization originating in the deep reticular dermis and wound edge.
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PMID:Substance P has a role in neurogenic mediation of human burn wound healing. 888 61

Upon activation nociceptors release neuropeptides in the skin provoking vasodilation and plasma protein extravasation in rodents, but only vasodilation in humans. Pivotal peptides in the induction of neurogenic inflammation comprise calcitonin gene-related peptide and substance P, the latter being suggested to act partly via degranulation of mast cells. In this study substance P and calcitonin gene-related peptide-induced vasodilation, protein extravasation, histamine release, and sensory effects were investigated simultaneously in human skin by dermal microdialysis. The vasodilatory prostaglandin E(2) and the mast cell activator codeine served as positive controls. Substance P and calcitonin gene-related peptide applied intradermally via large cut-off plasmapheresis capillaries induced dose-dependent local vasodilation, but only SP provoked protein extravasation in concentrations greater than 10(-9) M. Substance P-induced (10(-8)-10(-6) M) protein extravasation was not accompanied by histamine release and was unaffected by cetirizine (histamine H1 blocker, 200 microg per ml). Only the highest concentration of substance P (10(-5) M) induced significant histamine release. Neither neuropeptide caused any axon reflex erythema or any itch or pain sensation, whereas mast cell degranulation by codeine dose dependently provoked itch, flare, protein extravasation, and histamine release. In human skin calcitonin gene-related peptide and substance P induce vasodilation by a mechanism not involving histamine. No evidence for neuropeptide-induced activation of nociceptors was obtained. Our results suggest that endogenous calcitonin gene-related peptide and substance P have no acute sensory function in human skin. The lack of neurogenic protein extravasation in humans can most probably be attributed to low local concentrations of this neuropeptide still sufficient to exert trophic and immunomodulatory effects (10(-11) M), but too low to induce protein extravasation (10(-8) M) or even mast cell degranulation (10(-5) M). J Invest Dermatol 115:1015-1020 2000
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PMID:Acute effects of substance P and calcitonin gene-related peptide in human skin--a microdialysis study. 1112 Nov 35

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


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