Pain Centre Versus Arthritis & NIHR Nottingham Biomedical Research Centre, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.
Pain Centre Versus Arthritis & NIHR Nottingham Biomedical Research Centre, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.
Curr Opin Pharmacol. 2024 Oct;78:102477. doi: 10.1016/j.coph.2024.102477. Epub 2024 Aug 27.
Chronic pain is a major burden and the complexities of chronic pain pathophysiology, including both peripheral and central sensitisation mechanisms, involves multiple cell types (neuronal, immune, neuroimmune, and vascular) which substantially complicates the development of new effective analgesic treatments. The epoxy fatty acids (EpFAs), including the epoxyeicosatrienoic acids (EETs), are derived from the metabolism of polyunsaturated fatty acids (PUFAs) via the cytochrome P450 enzymatic pathway and act to shut-down inflammatory signalling and provide analgesia. The EpFAs are rapidly metabolised by the enzyme soluble epoxide hydrolase (sEH) into their corresponding diol metabolites, which recent studies suggest are pro-inflammatory and pro-nociceptive. This review discusses clinical and mechanistic evidence for targeting the sEH pathway for the treatment of pain.
慢性疼痛是一个主要的负担，其病理生理学的复杂性，包括外周和中枢敏化机制，涉及多种细胞类型（神经元、免疫、神经免疫和血管），这大大增加了新的有效镇痛治疗方法的开发难度。环氧脂肪酸（EpFAs），包括环氧二十碳三烯酸（EETs），来源于多不饱和脂肪酸（PUFAs）通过细胞色素 P450 酶途径的代谢，并起到抑制炎症信号和提供镇痛的作用。环氧脂肪酸被可溶性环氧水解酶（sEH）迅速代谢为其相应的二醇代谢物，最近的研究表明这些代谢物具有促炎和致痛作用。本综述讨论了靶向 sEH 途径治疗疼痛的临床和机制证据。
