A study of mechanism for antiallodynic effect of novel neuropeptide, APGWamide

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Intrathecal administration of APGWamide significantly attenuated mechanical and thermal allodynia in the rats with diabetic neuropathy. Induction of c-Fos-like immunoreactivity that was observed in the spinal dorsal horn of diabetic rat following innocuous thermal stimulation to the hind paw was inhibited by intrathecal administration of APGWamide. These antiallodynic effects of APGWamide were inhibited by simultaneous injection of a specific 5-HT1 receptor or specific alpha2 adrenoceptor antagonist. These results indicate that APGWamide have an antiallodynic activity, which may be mediated by serotonergic and/or noradrenergic descending pain inhibitory system. Furthermore, investigation of structure and activity relationship of APGWamide using C-terminal fragment peptides of APGWamide and analogue peptides of a single amino acid substitution at N-terminal amino acid residue of APGWamide has provided information of important structure of APGWamide for antiallodynic activity.