细胞色素P450与慢性疼痛：代谢及神经炎症机制*

Cytochrome P450 in Chronic Pain: Metabolism and Neuroinflammation*

摘要:

细胞色素 P450（Cytochrome P450, CYP450）属于一类可自身氧化的亚铁血红素蛋白家族，作为机体的关键代谢酶，在药物代谢过程中扮演着核心角色。部分CYP450家族成员在中枢神经系统特异性表达，通过调控内源性活性物质和精神类药物代谢，参与病理生理功能。近年研究揭示，特定CYP450亚型（如CYP2J6、CYP26A1、CYP2D6和CYP3A4）通过代谢内源性脂质介质（如类花生酸类物质）和外源性化合物（如临床药物），在炎症性疼痛和神经病理性疼痛的发生发展过程中发挥关键调控作用。然而，目前研究仍存在若干亟待解决的重要问题，如：其他CYP450家族成员在慢性疼痛中的作用尚未明确；不同亚型间可能存在的功能协同或拮抗效应有待阐明；个体遗传差异对疼痛感知和药物反应的影响机制仍需探索。本文系统梳理CYP450酶系的结构特征、组织分布及其代谢网络，重点评述其在慢性疼痛领域的研究进展，并展望靶向CYP450的疼痛治疗策略，旨在为开发精准镇痛方案提供新的思路和理论依据。

Abstract:

Cytochrome P450 (CYP450) belongs to a family of self-oxidizing heme proteins and serves as a key metabolic enzyme in the body, playing a central role in drug metabolism. Some CYP450 family members are specifically expressed in the central nervous system, where they regulate the metabolism of endogenous active substances and psychoactive drugs, thereby playing physiological and pathological functions. Recent studies have revealed that certain CYP450 subtypes (such as CYP2J6, CYP26A1, CYP2D6, and CYP3A4) play critical regulatory roles in the development of inflammatory and neuropathic pain by metabolizing endogenous lipid mediators (such as eicosanoid-like substances) and exogenous compounds (such as clinical drugs). However, several important questions remain unresolved: the roles of other CYP450 family members in chronic pain are still unclear; potential synergistic or antagonistic effects among different subtypes need to be elucidated; and the mechanisms by which individual genetic differences affect pain perception and drug response require further exploration. This paper systematically reviews the structural characteristics, tissue distribution, and metabolic networks of the CYP450 enzyme system, with a focus on recent advances in chronic pain research. It also discusses potential pain treatment strategies targeting CYP450, aiming to provide new ideas and theoretical foundations for developing precise analgesic approaches.