Possible involvement of beta-endorphin in docosahexaenoic acid-induced antinociception.

摘要

We have previously demonstrated that the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has an antinociceptive effect on various pain stimuli in a naloxone-reversible manner. In the present study, the role of the endogenous opioid peptide beta-endorphin in DHA-induced antinociception was examined. DHA-induced antinociception was abolished when mice were pretreated with the mu-opioid receptor antagonist beta-funaltrexamine (beta-FNA) and the delta-opioid receptor antagonist naltrindole, but not by the kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) in the acetic acid-induced writhing test. In the radioligand binding assay, DHA itself did not have affinity for mu- , delta- or kappa-opioid receptors. On the other hand, the pretreatment of anti-beta-endorphin antiserum inhibited DHA-induced antinociception. Furthermore, the intracerebroventricular injection of DHA dose-dependently reduced writhing behavior, and this effect was inhibited by d-Phe-Cys-Tyr-Orn-Thr-Pen-Thr-NH(2) (CTOP) and naltrindole, but not nor-BNI. beta-endorphin-induced antinociception was inhibited by the pretreatment of beta-FNA, but not naltrindole or nor-BNI, and its levels in plasma were increased by DHA treatment. These findings suggest that the induction of antinociception by DHA may partially involve the mu-opioid receptor via the release of beta-endorphin.