慢性疼痛的细胞因子微环境假(修回)uncode讲义.docVIP

慢性疼痛的细胞因子微环境假说 周利君，信文君，庞瑞萍，刘先国* （中山大学疼痛研究中心，广州 510080） 摘要 慢性疼痛常常伴有记忆和情感障碍， 严重影响病人的生活质量和工作能力，但机制不清。根据慢性疼痛常常伴有神经系统致炎细胞因子异常升高；在外周神经或中枢施以致炎细胞因子可模拟神经损伤引起的慢性疼痛和记忆情感障碍；致炎细胞因子可模拟神经损伤，持久改变神经元的兴奋性和突触可塑性，我们提出慢性疼痛细胞因子微环境假说：在神经损伤等强伤害性刺激的作用下，神经系统细胞因子微环境发生异常改变，即致炎细胞因子升高，而抗炎细胞因子减少，导致神经系统的结构和功能发生变化，引起慢性疼痛、认知和情感障碍。因此，防止或纠正细胞因子微环境的失衡可能从根本上预防和治疗慢性疼痛。 关键词：细胞因子；慢性疼痛；记忆障碍；抑郁；神经可塑性 NSFC-广东省联合基金重点项目（U1201223）The cytokine microenvironment hypothesis of chronic pain Xian-Guo Liu Pain research center of Sun Yat-sen University (Guangzhou, 510080) Abstract Chronic pain is often accompanied by memory deficits and emotional problem. The multiple neurological disorders destroy patient’s life and working ability, and underlying mechanisms are poorly understood. Here, we suggested a cytokine microenvironment hypothesis of chronic pain, based on the following clinical and experimental evidence: Overexpression of proinflammatory cytokines is reliably detected in human and animals with chronic pain; Administration of proinflammatory cytokines is sufficient to induce behavioral signs of chronic pain, memory deficits and depression; Proinflammatory cytokines are capable of remodeling the excitability of neurons and synaptic plasticity. We proposed that nerve injury might induce abnormal change of cytokine microenvironment in nervous system, i.e., an increase in proinflammatory cytokine and a decrease in anti-inflammatory ones, which may lead to chronic pain, memory deficits and depression by altering the function and structure of nervous system. Thus, blockage or correction of the abnormal change in cytokine microenvironment may fundamentally prevent or cure chronic pain. Key words: cytokines; chronic pain; memory deficits; depression; neuronal plasticity The work is supported by a grant from Natural Science Foundation of China -Guangdong joint project Corresponding author: liuxg@mail.sysu.edu.cn 1、前言 各种原因（创伤、化疗药物和糖尿病等）引起的外周神经损伤常常导致神经病理性疼痛，表现为痛超敏（痛阈下降），即非伤害性刺激（如正常的触、压、冷、热刺激）引起疼痛；痛反应增强和自发性疼痛。由于损伤愈合后数