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

Capsaicin cream is the first of a class of neuropeptide active agents to be introduced into dermatologic therapy. Capsaicin's effects appear primarily related to its ability to deplete the neuropeptide substance P from local sensory terminals in the skin. The use of capsaicin cream in the treatment of postherpetic neuralgia and psoriasis is discussed. I believe that capsaicin and other neuropeptide active agents may become important therapeutic modalities for the dermatologist in the near future.
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PMID:Capsaicin in the treatment of dermatologic disease. 243 89

The morphological and biochemical substrates of the severe pain in post-herpetic neuralgia (PHN) are unclear. This report is an autopsy study of a 67-year-old male with severe PHN during the last 5 years of his life over the right T7-8 dermatomes. The dorsal horn of the thoracic spinal cord of the affected side was atrophic from T4 to T8, with loss of both myelin and axons. Despite this, only the T8 ganglion was affected by fibrosis and cell loss and only the nerve roots at that level appeared affected. Markers of unmyelinated afferents (substance P), substantia gelatinosa neurons (opiate receptors), glial cells (glial fibrillary acidic protein), and descending spinal projections (dopamine-beta-hydroxylase and serotonin) were not different at affected versus non-affected spinal cord levels. The pain of PHN may result from the uninhibited activity of unmyelinated primary afferents as a result of the loss of myelinated afferent fibers and the possible presence of hypersensitive neurons in the dorsal horn.
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PMID:Post-herpetic neuralgia: post-mortem analysis of a case. 317 52

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

Capsaicin, the active principle of hot chili pepper, is thought to selectively stimulate unmyelinated C fibre afferent neurons and cause the release of substance P. Prolonged application of capsaicin reversibly depletes stores of substance P, and possibly other neurotransmitters, from sensory nerve endings. This reduces or abolishes the transmission of painful stimuli from the peripheral nerve fibres to the higher centres. In clinical studies of patients with post-hepatic neuralgia, diabetic neuropathy or osteoarthritis, adjunctive therapy with topical capsaicin achieved better relief than its vehicle in most studies. In a single trial, topical capsaicin in demonstrated similar efficacy to oral amitriptyline in patients with diabetic neuropathy. Topical capsaicin is not associated with any severe systemic adverse effects. However, stinging and burning, particularly during the first week of therapy, is reported by many patients. Topical capsaicin merits consideration as adjuvant therapy in conditions such as post-herpetic neuralgia, diabetic neuropathy and osteoarthritis, where the pain can be chronic and difficult to treat.
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PMID:Topical capsaicin. A review of its pharmacological properties and therapeutic potential in post-herpetic neuralgia, diabetic neuropathy and osteoarthritis. 853 59

A variety of pharmacologic approaches to the management of pain due to nerve damage have been tried, with mixed results. Sympathetically maintained pain responds most commonly to sympathetic nerve blocks. Oral nifedipine may be a useful adjunct. Many-but not all-neuropathic pain patients experience relief from low-dose tricyclic antidepressants. When those drugs are not sufficient, the addition of an anticonvulsant, systemic local anesthetic, or both, to the antidepressant may be useful. Neuropathic pain with a major cutaneous component may respond well to topical therapy with the Substance P depletor capsaicin to reduce elevated prostaglandin levels. Topical therapy is most commonly used as an adjunct to systemic drugs. There is now good evidence that early treatment of acute herpes neuralgia with famciclovir may be effective in reducing postherpetic neuralgia. The role of opioids in chronic nerve pain is unclear. Most patients do not respond to these drugs, and should not receive them. Many patients with chronic neuropathic or sympathetically maintained pain need detoxification from opioids, sedative-hypnotics, and muscle relaxants. Some patients cannot carry out normal activities of daily living without opioids, however, and function well while taking low-dose, regularly scheduled opioids. The prognosis for successfully managing neuropathic and sympathetically maintained pain is greatly improved if appropriate therapy is initiated early in the course of the pain. When patients do not respond adequately to initial drug therapy, referral to an interdisciplinary pain management program for evaluation may be in order. Many neuropathic and SMP patients have complex pain syndromes which are most effectively managed through a coordinated, interdisciplinary approach. Careful attention to medical, pharmacologic, psychologic, and physical factors are the hallmarks of this type of treatment. The drugs now available provide marked relief to the majority of patients when therapy includes careful attention to the various dimensions of the pain syndrome. Although consistently effective drug therapy for all neuropathic and sympathetically maintained pain is not yet available, the probability of new NMDA antagonists being introduced in the next few years offers promise.
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PMID:Analgesic drugs for neuropathic and sympathetically maintained pain. 885 42

Pain management for partial-thickness burns and split-thickness skin graft donor sites remains a persistent problem. Topical capsaicin (trans-b-methyl-N-vanillyl-noneamide) has been successful for pain relief in postherpetic neuralgia, arthritis, and diabetic neuropathy. It is thought to work by inhibiting type C cutaneous factors and by releasing substance P, which is essential for wound healing. To evaluate the effects of topical capsaicin treatment on burn wounds and donor sites, an in vitro study was designed to consider cytotoxic effects of commercial concentrations of capsaicin on keratinocytes and fibroblasts. Human keratinocytes and human fibroblasts were grown in tissue culture and exposed to varying concentrations of capsaicin (0.025% weight/volume to 0.2% weight/volume). In addition, fibroblast-seeded collagen matrixes were exposed to capsaicin to evaluate the compound's ability to cause cytotoxic effects beneath the surface. Keratinocyte growth was reduced 21% to 31% in commercial concentrations of capsaicin 0.025% to 0.20% weight/volume. Fibroblasts were reduced 5% to 10% during the first 6 hours of exposure to capsaicin and 30% after 24 hours across the full range of concentrations tested. At concentrations of at least 0.1% weight/volume, capsaicin penetrated the collagen matrixes, resulting in fibroblast degeneration not only on the surface but also in the inner layers. On the basis of the fact that capsaicin was demonstrated to be cytotoxic to keratinocytes and fibroblasts and on the basis of its known detrimental effect on wound healing, it does not appear that topical capsaicin is indicated for the treatment of burns.
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PMID:Toxic effects of capsaicin on keratinocytes and fibroblasts. 978 76

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

5% lidocaine medicated plasters are available for local treatment of neuropathic pain. Treatment is generally poorly effective but has few adverse effects, other than local erythema. Capsaicin is a natural chilli pepper extract that depletes sensory nerve endings of substance P, a pain neurotransmitter. It is authorised in the European Union for the treatment of nondiabetic neuropathic pain, in the form of cutaneous patches containing 8% capsaicin. Clinical evaluation of capsaicin patches does not include any trials versus lidocaine plasters. Eight double-blind trials have compared 8% capsaicin patches versus 0.04% capsaicin patches, 5 in postherpetic neuralgia, and 3 in HIV-related neuropathic pain. These trials are only vaguely described in the European Medicines Agency report. Taken separately, they yielded divergent results. It was only when some of the trials were pooled for analysis that any differences emerged between the two doses of capsaicin. The clinical implications are unclear, but efficacy is at best modest. Capsaicin is an irritant that frequently provokes pain and erythema at the site of patch application, and 3% of patients using the patches experienced transient arterial hypertension that the investigators attributed to this pain. Some pharmacological data suggest that repeated application of 8% capsaicin patches might provoke painful nerve damage in the long-term. Patch application and removal by a third party is delicate, due to the strong irritant potential of capsaicin. In practice, when a patient with neuropathic pain requires local treatment, in the absence of a better alternative, it is better to use lidocaine plasters, which are better tolerated and with which we have more experience.
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PMID:Capsaicin. Neuropathic pain: playing with fire.... 2093 41

Botulinum neurotoxin (BoNT) is usually used in physiatric practice in the treatment of spasticity and dystonia. Research involving both animal and human subjects has emerged suggesting potential benefits in painful neuropathic conditions. The animal data strongly support the use of BoNT in the treatment of sensitized pain states. BoNT is probably effective at treating postherpetic neuralgia, probably or possibly effective at treating postoperative/posttraumatic neuropathic pain, and probably effective at treating painful diabetic neuropathy. BoNT's proposed mechanism of action is described as decreasing sensitized nociception in four ways by (1) inhibiting glutamate release in peripheral tissues, (2) decreasing calcitonin gene-related peptide release in peripheral tissue, (3) decreasing transient receptor potential cation channel subfamily V member 1 trafficking to peripheral neuron cell membrane, and (4) decreasing substance P release in peripheral tissue. This review discusses pertinent cellular/animal basic science research in conjunction with clinical research with regard to the role of BoNT in treating neuropathic pain.
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PMID:Do botulinum toxins have a role in the management of neuropathic pain?: a focused review. 2266 Mar 69


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