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)

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

In the present experiments the role of unmyelinated sensory fibres in the mechanism of cutaneous inflammatory reactions under normal and pathological conditions has been studied in man and animals. Dye leakage responses to histamine, serotonin, compound 48/80, bradykinin and substance P were significantly reduced, while neurogenic inflammation was completely abolished in rats treated neonatally with capsaicin, as studied quantitatively by the Evans blue technique. Neurogenic inflammation could also be elicited by mustard oil in normally innervated human skin, but not in skin areas affected by herpes zoster or in a patient suffering from congenital analgesia. Repeated topical treatment of the skin with capsaicin (local desensitization) abolished the neurogenic inflammatory response for several days. Chemical pain sensitivity was strongly reduced, and thresholds for warmth and heat pain sensations were significantly elevated. Local capsaicin desensitization of the skin prevented whealing, flare and itch in patients with acquired cold and heat urticaria. The findings indicate that peptide-containing sensory nerves are involved in the mediation of chemogenic and heat pain, and possibly itch, and are responsible for initiation of the neurogenic inflammatory response. The results also provide direct evidence of the involvement of these particular sensory nerves in the modulation of the permeability-increasing effects of putative mediators of acute inflammatory reactions. It is concluded that, through modulation of cutaneous vascular reactions, peptidergic sensory nerves may play a hitherto unrecognized role in the pathomechanism of certain diseases of human skin.
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PMID:The modulation of cutaneous inflammatory reactions by peptide-containing sensory nerves. 241 73

Substance P (SP) acutely enhanced the plasma concentration of aldosterone in rats whose hypothalamo-hypophyseal-adrenal axis and renin-angiotensin system were pharmacologically interrupted. The maximal response was obtained with a dose of 100 micrograms/kg. A prolonged (7 days) subcutaneous infusion with SP (50 micrograms/kg/hr) caused a notable hypertrophy of zona glomerulosa cells associated with significant rises in both basal and angiotensin-stimulated plasma levels of aldosterone. Zona fasciculata and the blood concentration of corticosterone were not affected. These findings suggest that SP is specifically involved in the stimulation of the growth and secretory activity of the rat zona glomerulosa.
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PMID:Effects of substance P on the rat adrenal zona glomerulosa in vivo. 246 63

Continuing pain following herpes zoster is common in patients 60 years of age or older. Current treatments are generally unsatisfactory. The endogenous neuropeptide substance P is an important chemomediator of nociceptive impulses from the periphery to the central nervous system and has been demonstrated in high levels in sensory nerves supplying sites of chronic inflammation. In an attempt to alleviate the pain of 14 patients with postherpetic neuralgia, capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), known to deplete substance P, was applied topically to painful areas of skin for 4 weeks. Of the 12 patients completing this preliminary study, 9 (75%) experienced substantial relief of their pain. The only adverse reaction was an intermittent, localized burning sensation experienced by one patient with application of capsaicin. Although these results are preliminary, they suggest that topical application of capsaicin may provide a useful approach for alleviating postherpetic neuralgia and other syndromes characterized by severe localized pain.
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PMID:Treatment of chronic postherpetic neuralgia with topical capsaicin. A preliminary study. 361 58

A Helium-Neon (He-Ne) laser with a wavelength of 632.8 nm is known to have photobiological effects and is widely used for reducing the pain of herpes zoster and accelerating wound healing, however the cellular mechanism and effect of the He-Ne laser are poorly understood. The present study was designed to examine the influence of He-Ne laser irradiation on irritant and allergic contact dermatitis of the mouse ear and on histamine release from rat peritoneal mast cells. Irradiation was applied with a He-Ne laser (12.2 J/cm2) at 1 h, 10 min, 5 min and 0 min before, and 5 min, 6 hs and 24 hs after a challenge of an irritated contact dermatitis (ICD) or allergic contact dermatitis (ACD) was made on the right ears of ICR-mice. Twenty-four hours after the challenge, the swelling of the ear was measured with a dial thickness gauge, and the anti-inflammatory effect of He-Ne laser irradiation was expressed as an ear thickness ratio (ETR). Although the laser did not decelerate the ETR from ICD, the allergic response was decelerated. Irradiation at 5 min after the challenge of contact dermatitis increased the thickness ratio. Next, the influence of the He-Ne laser on histamine release from Wistar-rat peritoneal mast cells was observed. The spontaneous histamine release was inhibited by laser irradiation, while substance P and compound 48/80-induced histamine release were not inhibited. From these results, it can be suggested that He-Ne laser irradiation has an anti-inflammatory effect on cutaneous inflammation.
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PMID:Effect of a helium-neon laser on cutaneous inflammation. 866 2

Varicella zoster virus (VZV) causes varicella (chickenpox) as the primary infection and zoster (shingles) on reactivation from latency, often many years later. One of the most common and most severe sequela of zoster is postherpetic neuralgia (PHN). Apart from age, factors which predispose towards PHN are unknown. In the present study, the concentration of a variety of Th1 and Th2 cytokines in the serum of 30 zoster patients at the time of the acute disease were correlated with the subsequent development of PHN in nine of these patients, but no association was found. In addition, although some cytokines such as IFN-gamma, IL-6 and IL-8 were slightly raised in the zoster group compared with a group of normal healthy subjects of a similar age distribution, these differences only verged on significance. Antibody titres to VZV were raised in the zoster group compared with the controls but these did not differ between the patients who developed PHN and those who did not. Biopsies of zoster lesions were collected from nine patients. There were significantly fewer infiltrating lymphocytes in the lesions of the three patients who subsequently developed PHN compared with the six who did not, although the expression of the neuropeptide, substance P, did not differ between the two groups. It is possible that the poor inflammatory response at the time of the acute zoster may result in less effective containment of the VZV and more damage in the dermatome, thus contributing to the persistence of the neuralgia.
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PMID:Local immune responses and systemic cytokine responses in zoster: relationship to the development of postherpetic neuralgia. 1256 95

Human dorsal root ganglia (DRGs) were obtained during various procedures and processed for single and double in situ hybridisation using oligonucleotide probes complementary to three peptide mRNAs. Some postmortem ganglia were also analysed. In donor (unlesioned) DRGs 12.5% of the neuron profiles (NPs) were galanin mRNA-positive (mRNA(+)), 47.5% calcitonin gene-related peptide (CGRP) mRNA(+) and 32.7% substance P mRNA(+). The corresponding percentages for cervical/thoracic DRGs from patients suffering from severe brachial plexus injury were 32.8%, 57.4% and 34.5%, respectively. In these DRGs a high proportion of the galanin mRNA(+) NPs contained CGRP mRNA and substance P mRNA. In DRGs from a patient with migraine-like pain a comparatively small proportion expressed galanin, whereas in DRGs from a herpes zoster patient galanin mRNA(+) NPs were comparatively more frequent. The results from human postmortem DRGs revealed only weak peptide mRNA signals. The present results demonstrate that galanin is expressed in DRGs not only in a number of animal species including monkey as previously shown, but also in a considerable proportion of human DRG neurons, often together with CGRP and substance P, and mostly in small neurons. Thus, galanin may play a role in processing of sensory information, especially pain, in human DRGs and dorsal horn. However, to what extent a similarly dramatic upregulation of galanin expression can be seen after peripheral nerve lesion in man, as has been reported for rat, mouse and monkey, remains to be analysed.
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PMID:Galanin expression in adult human dorsal root ganglion neurons: initial observations. 1265 33

While the underlying pathophysiology of herpes zoster infection has been well characterised, many of the mechanisms relating to the subsequent development of post herpetic neuralgia (PHN) remain uncertain. The dorsal horn atrophy and reduction in skin innervation seen in PHN patients does not adequately explain many clinical features or the efficacy of a number of topical treatments. In the central nervous system the glia, their receptors and their secreted signalling factors are now known to have a major influence on neural function. In the peripheral nervous system, schwann cell activation in response to infection and trauma releases a number of neuroexcitatory substances. Activation of the nervi nervorum in the peripheral nervous system also leads to the release of calcitonin gene related peptide, substance P and nitric oxide. Schwann cell and/or nervi nervorum activation could be an additional mechanism of pain generation in PHN. Such a paradigm shift would mean that drugs useful in the treatment of glial cell activation such as naloxone, naltrexone, minocycline, pentoxifyllline, propentofylline, AV411 (ibudilast) and interleukin 10 could be useful in PHN. These drugs could be used systemically or even topically. High dose topical vitamin D would appear to offer particular promise because vitamin D has the ability to both reduce glial inflammation and reduce nitric oxide production.
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PMID:Post herpetic neuralgia, schwann cell activation and vitamin D. 1963 51