Wang Yuxin, Wagner Karen M, Morisseau Christophe, Hammock Bruce D
Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA 95616, USA.
J Pain Res. 2021 Jan 13;14:61-72. doi: 10.2147/JPR.S241893. eCollection 2021.
Chronic pain is a complicated condition which causes substantial physical, emotional, and financial impacts on individuals and society. However, due to high cost, lack of efficacy and safety problems, current treatments are insufficient. There is a clear unmet medical need for safe, nonaddictive and effective therapies in the management of pain. Epoxy-fatty acids (EpFAs), which are natural signaling molecules, play key roles in mediation of both inflammatory and neuropathic pain sensation. However, their molecular mechanisms of action remain largely unknown. Soluble epoxide hydrolase (sEH) rapidly converts EpFAs into less bioactive fatty acid diols in vivo; therefore, inhibition of sEH is an emerging therapeutic target to enhance the beneficial effect of natural EpFAs. In this review, we will discuss sEH inhibition as an analgesic strategy for pain management and the underlying molecular mechanisms.
慢性疼痛是一种复杂的病症，会对个人和社会造成重大的身体、情感和经济影响。然而，由于成本高昂、缺乏疗效以及安全问题，目前的治疗方法并不充分。在疼痛管理方面，对于安全、无成瘾性且有效的疗法存在明显未满足的医疗需求。环氧脂肪酸（EpFAs）作为天然信号分子，在炎症性和神经性疼痛感觉的介导中发挥关键作用。然而，它们的分子作用机制在很大程度上仍不为人所知。可溶性环氧化物水解酶（sEH）在体内能迅速将EpFAs转化为生物活性较低的脂肪酸二醇；因此，抑制sEH是增强天然EpFAs有益作用的一个新兴治疗靶点。在本综述中，我们将讨论抑制sEH作为一种疼痛管理的镇痛策略及其潜在的分子机制。
