The involvement of GPR40 ⁄ FFAR1 as a novel target of stress induced–chronic pain

Abstract

It has been accepted the fact that patients with chronic pain comorbid with depression or anxiety appeal profoundly severe pain condition more than healthful emotional condition. The critical treatment of chronic pain has not been appeared although noradrenergic and serotonergic neurons were discovered as a target of treatment such as depression or anxiety. Recently, the importance of function of the n–3 free fatty acids (FFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid is focused on the novel target of chronic pain. However, the mechanism has not been elucidated. The G–protein coupled receptor 40 ⁄ free fatty acid receptor 1 (GPR40 ⁄ FFAR1), a receptor of middle–long chain FFAs including DHA, distribute in the brain of human and rodents. We previously reported that the GPR40 ⁄ FFAR1 suppressed not only various pain stimuli via activation of endogenous pain regulation systems but also depression–like behavior. Our previous study demonstrated that the GPR40 ⁄ FFAR1 knock–out mice show the persistent of mecha­nical allodynia after hind–paw incision. Furthermore, the GPR40 ⁄ FFAR1 knock–out mice show the abnormal emotional behaviors. Our results suggested that the GPR40 ⁄ FFAR1 has the potential of the novel therapeutic target of stress–induced chronic pain.