Antinociceptive effect of continuous intrathecal administration of endomorphin-1

Endomorphin-1 is a novel endogenous opioid peptide with high affinity and selectivity for the mu-opioid receptor. Earlier results have shown that it causes antinociception in different pain tests, but its effect is short-lasting. The purpose of the present study was to investigate the antinociceptive potency of continuously administered endomorphin-1 on carrageenan-induced thermal hyperalgesia by means of a paw withdrawal test in awake rats. The possible interaction between endomorphin-1 and the C-terminal octapeptide of the novel endogenous peptide nocistatin (bPNP-3-8P) was examined in the same experimental set-up. Continuous administration of endomorphin-1 (0.1, 0.3, 1 or 2 microg/min for 60 min) did not influence the paw withdrawal latencies of the normal paws. On the inflamed side, endomorphin-1 dose-dependently decreased the thermal hyperalgesia during continuous administration. The cessation of administration resulted in a gradual decrease in the antinociceptive effect of endomorphin-1. bPNP-3-8P (0.003-30 microg, administered cumulatively) significantly decreased the heat hyperalgesia at higher doses (3 and 30 microg). Continuous administration of bPNP-3-8P (0.03, 0.1 and 1 microg/min) did not potentiate the antinociceptive effect of endomorphin-1; instead, it even shortened the duration of its effect. The results demonstrate that continuous administration of endomorphin-1 is an effective method of inhibiting thermal hyperalgesia in rats. Furthermore, the fragment bPNP-3-8P itself has low antinociceptive potency and does not potentiate the antinociceptive effect of endomorphin-1 under these circumstances.