Attenuation of inflammatory and neuropathic pain behaviors in mice through activation of free fatty acid receptor GPR40

Molecular Pain

Atsuro Miyata³  Kazunori Arita⁵  Megumu Yoshimura⁴  Seiji Shioda¹  Tatsuki Oyoshi⁵  Toshihide Asada³  Jun Watanabe¹  Tomoya Nakamachi²  Takashi Kurihara³  Prasanna Karki³ 

[1] Department of Anatomy, Showa University, School of Medicine, 1-5-8 Hatanodai, Tokyo 142-8555, Shinagawa-ku, Japan;Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, 3190-Gofuku, Toyama 930-8555, Japan;Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City 890-8544, Kagoshima, Japan;Graduate School of Health Sciences, Kumamoto Health Science University, 325 Izumi-machi, Kumamoto 861-5598, Japan;Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City 890-8544, Kagoshima, Japan

关键词: Whole-cell patch-clamp;    Spinal nerve ligation;    Spinal cord;    Hyperalgesia;    FFAR1;    FFA1;    Complete Freund’s adjuvant;    Carrageenan;    Allodynia;   

Others  :  1130926
DOI  :  10.1186/s12990-015-0003-8

 received in 2014-10-28, accepted in 2015-01-26,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Karki et al.; licensee BioMed Central.

【 图 表 】

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