title: Involvement of GPR40, a long-chain free fatty acid receptor, in the production of central post-stroke pain after global cerebral ischemia.
abstract: Central post-stroke pain (CPSP), one of the complications of cerebral ischemia and neuropathic pain syndrome, is associated with specific somatosensory abnormalities. Although CPSP is a serious problem, detailed underlying mechanisms and standard treatments for CPSP are not well established. In this study, we assessed the role of GPR40, a long-chain fatty acid receptor, showing anti-nociceptive effects, in CPSP. We also examined the role of astrocytes in CPSP due to their effects in mediating the release of polyunsaturated fatty acids, which act as potential GPR40 ligands. The aim of this study was to determine the interactions between CPSP and astrocyte/GPR40 signaling. Male ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). The development of hind paw mechanical hyperalgesia was measured after BCAO using the von Frey test. Neuronal damage was estimated by histological analysis on day 3 after BCAO. The thresholds for hind paw mechanical hyperalgesia were significantly decreased on days 1-28 after BCAO when compared with those of pre-BCAO assessments. BCAO-induced mechanical hyperalgesia was significantly decreased by intracerebroventricular injection of docosahexaenoic acid or GW9508, a GPR40 agonist; furthermore, these effects were reversed by GW1100, a GPR40 antagonist. The expression levels of glial fibrillary acidic protein, an astrocytic marker, and some free fatty acids were significantly decreased 5h after BCAO, although no effects of BCAO were noted on hypothalamic GPR40 protein expression. Our data show that BCAO-induced mechanical hyperalgesia is possible to be regulated by astrocyte activation and stimulation of GPR40 signaling.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Harada
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Haruna
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Fuka
authors.initials: F
authors.lastname: Aizawa
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Matsuura
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamoto
authors.affiliation: Biochemical Toxicology Laboratory, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Biochemical Toxicology Laboratory, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Kasuya
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan. Electronic address: stoku@pharm.kobegakuin.ac.jp.
authors.forename: Shogo
authors.initials: S
authors.lastname: Tokuyama
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008744:Methylamines / Q000494:pharmacology; D051379:Mice; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; C473036:Ffar1 protein, mouse; C515630:GW9508; D008744:Methylamines; D011422:Propionates; D043562:Receptors, G-Protein-Coupled; D004281:Docosahexaenoic Acids
keywords: Astrocyte; Central post-stroke pain (CPSP); Docosahexaenoic acid (DHA); Docosahexaenoic acid (PubChem CID: 6440152); GPR40; Global ischemia (BCAO)