title: Possible involvement of β-endorphin in docosahexaenoic acid-induced antinociception.
abstract: 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 β-endorphin in DHA-induced antinociception was examined. DHA-induced antinociception was abolished when mice were pretreated with the μ-opioid receptor antagonist β-funaltrexamine (β-FNA) and the δ-opioid receptor antagonist naltrindole, but not by the κ-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 μ- , δ- or κ-opioid receptors. On the other hand, the pretreatment of anti-β-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. β-endorphin-induced antinociception was inhibited by the pretreatment of β-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 μ-opioid receptor via the release of β-endorphin.
authors.affiliation: Department of Clinical Pharmacy, Kobe Gakuin University, School of Pharmaceutical Sciences, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishinaka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ambo
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Mankura
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Kasuya
authors.forename: Shogo
authors.initials: S
authors.lastname: Tokuyama
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology; D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D013997:Time Factors; D001615:beta-Endorphin / Q000097:blood / Q000378:metabolism*
chemical_list: D000700:Analgesics; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D004281:Docosahexaenoic Acids; D001615:beta-Endorphin; D019342:Acetic Acid