Sigma-1受体在慢性疼痛中的调节作用及其神经机制

Sigma-1受体（sigma-1 receptor, Sig-1R）属于配基依赖性的分子伴侣蛋白质，广泛表达于神经系统的多个区域，并可通过结合多种类型的阳离子通道及G蛋白偶联受体（G-protein-coupled receptors, GPCRs）对它们介导的细胞内效应进行调控，或是在内质网和线粒体相关膜结构上对细胞内Ca2+的稳态进行调节。在包括神经病理性疼痛、炎性疼痛及内脏痛的多种类型慢性疼痛疾病中，Sig-1R均可不同程度地参与痛觉过敏的调控作用。针对不同的慢性疼痛疾病类型，Sig-1R可表现功能相反的调控作用，即在大部分慢性疼痛疾病中表现对疼痛发生发展的促进作用，而在外伤性脑损伤为代表的部分疾病中表现抑制疼痛，缓解损伤神经的作用。在Sig-1R调节慢性疼痛的调节神经机制方面，Sig-1R一方面可通过对痛觉信息的传递，包括神经元的内在兴奋性以及神经元间突触传递调节两个方面进行直接的调节，另一方面可通过对各类细胞因子、趋化因子以及包括星形胶质细胞和小胶质细胞在内的神经免疫细胞活动的调节影响炎症反应过程，并间接影响疼痛反应。本文就Sig-1R参与不同类型慢性神经系统性疾病的调控作用做一综述。

Regulation of the Sigma-1 Receptor on Chronic Pain and Its Neuromechanism

Sigma-1 receptor (Sig-1R) is a ligand-regulated chaperone protein widely expressed in multiple regions of the nervous system. It mediates intracellular effects of several types of ion channels and G protein coupled receptors (GPCRs) by binding them, and regulates intracellular Ca2+ homeostasis on the endoplasmic reticulum and mitochondrial-related membrane structures. In many types of chronic pain diseases including neuropathic pain, inflammatory pain and visceral pain, Sig-1R participates in the regulation of hyperalgesia to varying degrees. For different types of chronic pain, Sig-1R exhibits opposite functions, that is, it promotes the development of pain in most chronic pain diseases, while it inhibits pain reaction and relieves nerve damage in some diseases represented by traumatic brain injury. The neuromechanism of Sig-1R in chronic pain is two-fold. On the one hand, it directly modulates the transmission of pain information through the neuronal intrinsic excitability and synaptic transmission between neurons. On the other hand, it affects the inflammatory response process through cytokines, chemokines, and neuroimmune cell activities including astrocytes and microglia, and thereby modulates the pain response indirectly. Herein we present a review of the regulatory role of Sig 1R in different types of chronic neurological systemic diseases.