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

Rationale 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.