Popiolek-Barczyk Katarzyna, Mika Joanna
Institute of Pharmacology, Polish Academy of Sciences, Department of Pain Pharmacology, 12 Smetna Str., 31-343 Krakow, Poland.
Curr Med Chem. 2016;23(26):2908-2928. doi: 10.2174/0929867323666160607120124.
The microglia, once thought only to be supporting cells of the central nervous system (CNS), are now recognized to play essential roles in many pathologies. Many studies within the last decades indicated that the neuro-immune interaction underlies the generation and maintenance of neuropathic pain. Through a large number of receptors and signaling pathways, the microglial cells communicate with neurons, astrocytes and other cells, including those of the immune system. A disturbance or loss of CNS homeostasis causes rapid responses of the microglia, which undergo a multistage activation process. The activated microglia change their cell shapes and gene expression profiles, which induce proliferation, migration, and the production of pro- or antinociceptive factors. The cells release a large number of mediators that can act in a manner detrimental or beneficial to the surrounding cells and can indirectly alter the nociceptive signals. This review discusses the most important microglial intracellular signaling cascades (MAPKs, NF-kB, JAK/STAT, PI3K/Akt) that are essential for neuropathic pain development and maintenance. Our objective was to identify new molecular targets that may result in the development of powerful tools to control the signaling associated with neuropathic pain.
小胶质细胞，曾被认为仅是中枢神经系统（CNS）的支持细胞，现在则被认识到在许多病理过程中发挥着重要作用。过去几十年的许多研究表明，神经免疫相互作用是神经性疼痛产生和维持的基础。通过大量的受体和信号通路，小胶质细胞与神经元、星形胶质细胞及其他细胞（包括免疫系统的细胞）进行交流。中枢神经系统稳态的紊乱或丧失会导致小胶质细胞的快速反应，小胶质细胞会经历一个多阶段的激活过程。被激活的小胶质细胞会改变其细胞形态和基因表达谱，进而诱导增殖、迁移以及产生促痛或抗痛因子。这些细胞会释放大量的介质，这些介质对周围细胞的作用可能是有害的或有益的，并且可以间接改变伤害性信号。本综述讨论了对神经性疼痛的发生和维持至关重要的最重要的小胶质细胞内信号级联反应（丝裂原活化蛋白激酶、核因子κB、Janus激酶/信号转导子和转录激活子、磷脂酰肌醇-3激酶/蛋白激酶B）。我们的目标是确定可能会促成开发强大工具以控制与神经性疼痛相关信号传导的新分子靶点。
