Endogenous endomorphin-2 contributes to spinal ĸ-opioid antinociception.

Multiple opioid receptor (OR) types and endogenous opioid peptides exist in the spinal dorsal horn and there may be interactions among these receptor types that involve opioid peptides. In a previous study we observed that antinociceptive effects of the selective κ-opioid receptor (κOR) agonist, U50,488H, was attenuated in μ-opioid receptor (μOR) knockout mice as compared to wild-type mice when administered spinally. This suggests that an interaction between κORs and μORs exits in the spinal cord. The present study was aimed at investigating whether endogenous opioid peptides were involved in such interaction. We examined whether the presence of antibodies to endogenous opioid peptides, endomorphin-2, met-enkephalin and dynorphin A affected the antinociceptive effects of spinal U50,488H in rats. The tail-flick test was used to assess pain thresholds. The increase in tail-flick latency after spinal U50,488H was attenuated when the rats were pretreated intrathecally with antiserum against endomorphin-2. Pretreatments with antisera against met-enkephalin and dynorphin A had no effect on U50,488H antinociception. The antisera alone did not affect pain threshold. The results suggest that endomorphin-2, an endogenous opioid peptide highly selective to the μOR, plays a role in antinociception induced by κOR activation in the spinal cord.