title: Attenuation of inflammatory and neuropathic pain behaviors in mice through activation of free fatty acid receptor GPR40.
abstract: BACKGROUND
  The G-protein-coupled receptor 40 (GPR40) is suggested to function as a transmembrane receptor for medium- to long-chain free fatty acids and is implicated to play a role in free fatty acids-mediated enhancement of glucose-stimulated insulin secretion from pancreas. However, the functional role of GPR40 in nervous system including somatosensory pain signaling has not been fully examined yet.
  
  
  RESULTS
  Intrathecal injection of GPR40 agonist (MEDICA16 or GW9508) dose-dependently reduced ipsilateral mechanical allodynia in CFA and SNL models and thermal hyperalgesia in carrageenan model. These anti-allodynic and anti-hyperalgesic effects were almost completely reversed by a GPR40 antagonist, GW1100. Immunohistochemical analysis revealed that GPR40 is expressed in spinal dorsal horn and dorsal root ganglion neurons, and immunoblot analysis showed that carrageenan or CFA inflammation or spinal nerve injury resulted in increased expression of GPR40 in these areas. Patch-clamp recordings from spinal cord slices exhibited that bath-application of either MEDICA16 or GW9508 significantly decreased the frequency of spontaneous excitatory postsynaptic currents in the substantia gelatinosa neurons of the three pain models.
  
  
  CONCLUSIONS
  Our results indicate that GPR40 signaling pathway plays an important suppressive role in spinal nociceptive processing after inflammation or nerve injury, and that GPR40 agonists might serve as a new class of analgesics for treating inflammatory and neuropathic pain.
authors.affiliation: Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, 890-8544, Japan. prasannakarki7@gmail.com.|Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, 890-8544, Japan. prasannakarki7@gmail.com.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Karki
authors.affiliation: Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, 890-8544, Japan. tkmphm10@m.kufm.kagoshima-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurihara
authors.affiliation: Department of Anatomy, Showa University, School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. nakamachi@med.showa-u.ac.jp.|Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, 3190-Gofuku, Toyama, 930-8555, Japan. nakamachi@med.showa-u.ac.jp.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakamachi
authors.affiliation: Department of Anatomy, Showa University, School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. watanabe@med.showa-u.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Watanabe
authors.affiliation: Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, 890-8544, Japan. k9556456@kadai.jp.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Asada
authors.affiliation: Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, 890-8544, Japan. tatsuki@m2.kufm.kagoshima-u.ac.jp.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Oyoshi
authors.affiliation: Department of Anatomy, Showa University, School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. shioda@med.showa-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
authors.affiliation: Graduate School of Health Sciences, Kumamoto Health Science University, 325 Izumi-machi, Kumamoto, 861-5598, Japan. yoshimum@kumamoto-hsu.ac.jp.
authors.forename: Megumu
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, 890-8544, Japan. karita@m2.kufm.kagoshima-u.ac.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Arita
authors.affiliation: Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, 890-8544, Japan. amiyata@m3.kufm.kagoshima-u.ac.jp.
authors.forename: Atsuro
authors.initials: A
authors.lastname: Miyata
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D008744:Methylamines / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013127:Spinal Nerves / Q000187:drug effects / Q000378:metabolism
chemical_list: D000700:Analgesics; D005230:Fatty Acids, Nonesterified; C473036:Ffar1 protein, mouse; C515630:GW9508; D008744:Methylamines; D011422:Propionates; D043562:Receptors, G-Protein-Coupled