GABA Puts a Stop to Pain
GABA Puts a Stop to Pain
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DOI：
10.2174/1568007043336716
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发表时间：
2004-01-01
影响因子：
3
通讯作者：
Ohara, P. T.
中科院分区：
文献类型：
--
作者：
Jasmin, L.;Wu, M., V;Ohara, P. T.
缺乏抑制，特别是由γ-氨基丁酸（GABA）介导的抑制，中枢神经系统（CNS）的主要抑制性递质，是许多疼痛状态的原因。直到最近，很少有GABA作用药物可用，并且主要用于缓解肌肉痉挛，焦虑和癫痫，但很少用于疼痛。GABA的基本代谢途径是众所周知的，我们现在开始了解这种神经递质在复杂的疼痛回路中的功能，特别是在神经损伤的情况下。目前正在开发针对GABA转运蛋白以及GABA相关酶和受体的镇痛化合物。一些GABA类似物通过抑制离子通道起作用，这是一种有助于其镇痛作用的性质。然而，尽管在开发新化合物方面取得了相当大的进展，但全身作用的GABA能药物的使用受到对与疼痛有关的系统以外的系统的不希望的副作用以及在大脑的某些区域中GABA可以增强而不是减轻疼痛的事实的限制。靶向GABA受体和转运蛋白亚型的新药的出现以及使用新开发的递送系统（如鞘内泵和病毒载体）靶向神经系统特定区域的可能性可能有助于规避这些问题。
A lack of inhibition, particularly that mediated by gamma-amino butyric acid (GABA), the main inhibitory transmitter of the central nervous system (CNS), is responsible for many pain states. Until recently, few GABA acting drugs were available and were prescribed mostly for relieving muscle spasms, anxiety and epilepsy, but rarely for pain. The basic metabolic pathway of GABA is well known and we are now beginning to understand the function of this neurotransmitter in the complex circuitry underlying pain, especially in the context of nerve injury. Analgesic compounds are now being developed targeting GABA transporters as well as GABA associated enzymes and receptors. Some GABA analogs act by inhibiting ion channels, a property that contributes to their analgesic effects. However, despite considerable progress in developing new compounds, the use of systemically acting GABAergic drugs is limited by unwanted side-effects on systems other than those involved in pain, and by the fact that in certain areas of the brain, GABA can enhance rather than reduce pain. The advent of new drugs targeting subtypes of GABA receptors and transporters and the possibility of using newly developed delivery systems, such as intrathecal pumps and viral vectors, to target specific areas of the nervous system will likely help circumvent these problems.