摘要
背景痛觉敏化的机制尚未清楚，以往研究集中在神经系统兴奋性增强，近年来抑制性功能下调在痛觉敏化中的作用引起关注。中枢神经系统抑制性受体^y氧基丁酸A（γ-aminobutyricacidA，GABA。）受体的标志性蛋白之一钾-氯离子协同转运体2（K＋-Cl-cotransporter2，KCC2）在神经元从抑制到兴奋的转变中起了重要作用。KCC2通过影响Cl-的浓度来影响吖一氨基丁酸／甘氨酸所介导的抑制作用，进而影响神经系统兴奋性。目的就KCC2在痛觉敏化发生过程中的作用及相关通路进行综述。内容多种细胞外信号可以激活小胶质细胞并且引起P2X4Rs的上调；P2X4Rs的激活触发脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）从小胶质细胞的释放；BDNF到神经元的酪氨酸蛋白激酶B受体（tyrosine kinase Breceptor，TrkB）信号通路改变KCC2的功能，导致神经元Cl-外排能力的降低，从而抑制1弓瓦基丁酸／甘氨酸所介导的抑制作用。趋向研究KCC2参与痛觉敏化形成的机制，为痛觉过敏化的治疗提供新的靶点。
Background The underlying mechanism of hyperalgia is still remained unclear. Many previous researches focused on the up-regulation of excitable neurotransmitters. Recently it has been noticed that the expression of potassium-chloride co- transporter2 （KCC2）, a functional protein of ^-aminobutyric acid A （GABAA） receptors, was altered during the development of hyperalgesia, which caused the neurons from inhibition to excitation.The KCC2 establishes the low intraneuronal C1- levels required for the hyperpolarizing inhibitory postsynaptic potentials mediated by ionotropic GABA~ receptors and glycine （Gly） receptors. Objective The role of KCC2 in pain sensitization and it＇s pathways is reviewed. Content Various extracellular signals may activate microglia and upregulate P2X4Rs. P2X4R activation triggers the release of brain-derived neurotrophic factor （BDNF） from microglia. BDNF-tyrosine kinase B receptor （TrkB） signaling alters KCC2 function leading to a reduced C1- extrusion capacity which dampens GABAA receptor/Gly receptor mediated inhibition. Trend Understanding the molecular mechanism of KCC2 in hyperalgesia can provide novel targets for therapeutic approaches.
出处
《国际麻醉学与复苏杂志》
CAS
2015年第2期170-173,181,共5页
International Journal of Anesthesiology and Resuscitation
基金
国家自然科学基金（81471134）
