title: [Elucidation of mechanisms underlying docosahexaenoic acid-induced antinociception].
abstract: Docosahexaenoic acid (DHA), a predominant of n-3 polyunsaturated fatty acids (n-3 PUFA), has numerous beneficial physiological effects, including neuroprotection and cardiovascular protection. Recently, a possible involvement of n-3 PUFA in pain control has gathered considerable attention because numerous studies have reported a regulatory role of n-3 PUFAs. However, the mechanisms underlying how DHA exerts antinociceptive effect remain unknown. Here, we performed elucidation of mechanisms underlying DHA-induced antinociception. DHA administration dose-dependently exerted an antinociceptive effect. This effect was abolished by pretreated with the β-funaltrexamine (β-FNA), a μ-opioid receptor antagonist, and the nartrindole (NTI), a δ-opioid receptor antagonist, but not by the nor-binaltorphimine (nor-BNI), a κ-opioid receptor antagonist. In the radioligand binding assay, DHA itself did not have the affinity for μ-, δ- and κ- opioid receptor. Furthermore, the pretreatment of anti β-endorphin antiserum inhibited DHA-induced antinociception. The plasma levels of β-endorphin increased 30 min after DHA administration. The β-endorphin immunoreactivity in the brain increased at 30 min after DHA treatment. Expression of GPR40 protein was widely observed in the brain as well as the spinal cord. The intracerebroventricular but not intrathecal injection of DHA and GW9508, a GPR40/GPR120 agonist, significantly reduced formalin-induced pain behavior. The β-endorphin immunoreactivity in the brain increased at 10 and 20 min after intracerebroventricular injection of DHA and GW9508. These findings suggest that DHA-induced antinociception via β-endorphin release may be mediated through GPR40 signaling in the supraspinal area.
authors: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University.
authors: Takashi
authors: T
authors: Nishinaka
authors: Kengo
authors: K
authors: Matsumoto
authors: Kazuo
authors: K
authors: Nakamoto
authors: Akihiro
authors: A
authors: Anbo
authors: Mitsumasa
authors: M
authors: Mankura
authors: Yutaka
authors: Y
authors: Koyama
authors: Shogo
authors: S
authors: Tokuyama
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D001615:beta-Endorphin / Q000378:metabolism / Q000502:physiology
chemical_list: D000700:Analgesics; D015525:Fatty Acids, Omega-3; C473036:Ffar1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D004281:Docosahexaenoic Acids; D001615:beta-Endorphin