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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1984 Jun;82(2):381–388. doi: 10.1111/j.1476-5381.1984.tb10773.x

Hyperalgesia produced by intrathecal substance P and related peptides: desensitization and cross desensitization.

S M Moochhala, J Sawynok
PMCID: PMC1987042  PMID: 6203593

Abstract

The hyperalgesic effect of intrathecally administered substance P (SP), physalaemin, eledoisin and eledoisin-related peptide (ERP) was investigated in the rat tail flick test. Hyperalgesia produced by SP (2.5-15 micrograms, 1.9-11 nmol) was maximal 10-20 min after injection, lasted 30 min and was dose-related. The effect was mimicked by all of the peptides examined. The rank order of potency was physalaemin greater than SP greater than eledoisin greater than ERP. Desensitization to the hyperalgesic effect of SP was produced by three repeated intrathecal injections. Rats desensitized to SP no longer responded to physalaemin or ERP, indicating cross-desensitization. Phentolamine continued to produce hyperalgesia following such desensitization. The demonstration of a hyperalgesic effect for SP provides further support for a role for SP in nociceptive transmission. The receptor mediating this effect appears to be a SP-P subtype. Cross-desensitization between peptides suggests an action on the same receptor.

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Selected References

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