Chloride regulation in the pain pathway.
Chloride regulation in the pain pathway.
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DOI：
10.1016/j.brainresrev.2008.12.015
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发表时间：
2009-04
影响因子：
--
通讯作者：
Prescott SA
中科院分区：
文献类型：
--
作者：
Price TJ;Cervero F;Gold MS;Hammond DL;Prescott SA
Melzack和Wall的疼痛门控制理论为脊髓抑制在内源性疼痛控制中的作用奠定了理论基础。虽然门控理论是基于脊髓抑制是动态调节的这一概念，但抑制调节的潜在机制已经被证明比Melzack和Wall所能想象的要复杂得多。最近的证据表明，一种非常敏感的调节形式涉及阴离子平衡电位（Eanion）的变化，其随后影响快速突触抑制介导的GABAA，并在较小程度上影响甘氨酸受体激活，即原型配体门控阴离子通道。阳离子-氯共转运蛋白（特别是NKCC1和KCC2）作为在阴离子的动态调节中起关键作用的蛋白质已经出现，而阴离子又在周围炎症或神经损伤后的痛觉过敏和异常性疼痛中起关键作用。这篇综述总结了这一领域的知识现状，特别关注这些发现与痛觉过敏和异位性痛的内源性机制的关系，以及基于细胞内Cl -梯度调节或靶向GABAA受体的药物干预的治疗方法的潜在应用
Melzack and Wall’s Gate Control Theory of Pain laid the theoretical groundwork for a role of spinal inhibition in endogenous pain control. While the Gate Control Theory was based on the notion that spinal inhibition is dynamically regulated, mechanisms underlying the regulation of inhibition have turned out to be far more complex than Melzack and Wall could have ever imagined. Recent evidence indicates that an exquisitely sensitive form of regulation involves changes in anion equilibrium potential (Eanion), which subsequently impacts fast synaptic inhibition mediated GABAA, and to a lesser extent, glycine receptor activation, the prototypic ligand gated anion channels. The cation-chloride co-transporters (in particular NKCC1 and KCC2) have emerged as proteins that play a critical role in the dynamic regulation of Eanion which in turn appears to play a critical role in hyperalgesia and allodynia following peripheral inflammation or nerve injury. This review summarizes the current state of knowledge in this area with particular attention to how such findings relate to endogenous mechanisms of hyperalgesia and allodynia and potential applications for therapeutics based on modulation of intracellular Cl− gradients or pharmacological interventions targeting GABAA receptors
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影响因子：
5.3
作者：
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通讯作者：
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作者：
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