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

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Abstract
1 The hyperalgesic effect of intrathecally administered substance P (SP), physalaemin, eledoisin and eledoisin-related peptide (ERP) was investigated in the rat tail flick test. 2 Hyperalgesia produced by SP (2.5–15 μg, 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 > SP > eledoisin > ERP. 3 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. 4 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.