ストレスによる慢性疼痛形成機構における脳内脂肪酸-GPR40/FFAR1シグナルの関与

抄録

Chronic stress has been shown to exacerbate pain conditions. However, the details mechanism remains unclear. Previously, we have demonstrated that docosahexaenoic acid (DHA), one of n-3 polyunsaturated fatty acids (PUFAs), suppressed pain through activation of G-protein-coupled receptor 40 (GPR40)/free fatty acid receptor (FFAR) 1. More recently, we found that repeated social defeat-stressed mice showed pain chronicity after paw-incision, and this pain chronicity was exacerbated by infusion of the GPR40/FFAR1 antagonist, GW1100 or GPR40/FFAR1 knockout mice. In the brain of this stressed mice with pain, the phosphatidylcholines with DHA and other PUFAs were remarkably decreased compared to non-stressed mice. Oral DHA supplementation was improved stress-induced pain chronicity. Furthermore, the n-3 fatty acid deficient mice showed exacerbation of pain after repeated stress. These results indicated that chronic stress may directly affect brain lipid composition, the related changes could be involved in chronic pain development. Our findings suggested that n-3 fatty acids, particularly DHA, are useful as a potential therapeutic target for stress-induced chronic pain. In this symposium, we would like to discuss the role of brain n-3 fatty acids-GPR40/FFAR1 signaling in stress-induced pain chronicity.