, Volume 235, Issue 8, pp 2335–2347 | Cite as

The involvement of free fatty acid-GPR40/FFAR1 signaling in chronic social defeat stress-induced pain prolongation in C57BL/6J male mice

  • Fuka Aizawa
  • Kazuo Nakamoto
  • Shogo TokuyamaEmail author
Original Investigation



Depression and anxiety can cause the development of chronic pain. However, the mechanism of chronic pain induced by emotional dysfunction is still unknown. Previously, we demonstrated that the G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFAR1) signaling in the brain is related to regulation of both pain and emotion. In the present study, we proved that the role of GPR40/FFAR1 signaling in the development of chronic pain is induced by emotional dysfunction.


Repeated social defeat (SD)-stressed mice showed the impairment of social interaction and anxiety behavior. These mice also caused pain prolongation after paw-incision comparison with non-SD mice. This pain prolongation was markedly continued by infusion of the GPR40/FFAR1 antagonist, GW1100 during SD stress but not non-SD stress. Although, infusion of the GW1100 during SD stress did not cause deterioration of the emotional behavior. Furthermore, GW1100-treated SD-mice showed strong tendency of emotional dysfunction after paw incision.


Our findings indicate that the dysfunction of fatty acids-GPR40/FFAR1 signaling in the brain underlying stress condition might be related to the development of chronic pain.


Chronic pain Emotional dysfunction GPR40/FFAR1 Free fatty acid 


Funding information

Part of this experiment was supported by the Takeda Science foundation, by Grants-in-Aid and Special Coordination Funds from the Kobe Gakuin University Joint Research (A), and a Grant-in-Aid for Scientific Research (C) (15K10566) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Compliance with ethical standards

Ethical approval of the study protocol

This study was conducted in accordance with the Guiding Principles for the Care and Use of Laboratory Animals adopted by the Japanese Pharmacological Society. The Ethical Committee for Animal Experimentation of the Kobe Gakuin University approved the experiments (approval number: 17-10, Kobe, Japan).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

213_2018_4930_MOESM1_ESM.docx (22 kb)
ESM 1 (DOCX 22 kb)
213_2018_4930_MOESM2_ESM.pptx (341 kb)
ESM 2 (PPTX 341 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Clinical Pharmacy, School of Pharmaceutical SciencesKobe Gakuin UniversityKobeJapan

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