MMPs在疼痛和吗啡耐受中的作用

Role of Matrix Metalloproteinases in Pain and Morphine Tolerance

基质金属蛋白酶家族(matrix metalloproteinases,MMPs)是一类钙、锌依赖性内肽酶。MMPs共有28个成员,能降解细胞外基质的胶原成分,参与调控不同类型细胞的迁移、应激反应等。近年发现,MMP-9和MMP-2分别参与慢性神经损伤早期和后期痛觉高敏的形成和维持,是产生神经病理性痛的重要机制。此外,急性和慢性吗啡应用后也诱发MMP-9和MMP-2生成,减弱其镇痛作用,参与导致吗啡药物耐受。这些发现不但促进了疼痛机制理论的阐明,而且为治疗疼痛和阿片类药物副作用提供了新的路径。

The matrix metalloproteinases （MMPs） constitute a family of both zinc- and calcium-dependent endopeptidases. The MMPs include 28 MMP members, function in degrading the extracellular matrix collagen components and regulating different types of cells migration and stress response. Studies show that after chronic nerve injury, MMP-9 and MMP-2 are involved in the formation and maintenance of hyperalgesia, which is an important mechanism for inducing neuropathic pain. Besides, acute or chronic morphine application induces an increase of MMP-9 and MMP-2, which can weaken the analgesic effect of morphine and then lead to opioid toler- ance. These findings not only contribute to elucidate the mechanism of pain theory, but also provide a new path for the treatment of pain and opioid side effects.