Kalso Eija
University of Helsinki, Institute of Clinical Medicine, Pain Clinic, Department of Anaesthesia and Intensive Care Medicine, Helsinki University Central Hospital, P.O. Box 340, FIN-00029 HUS, Finland.
Curr Pharm Des. 2005;11(23):3005-11. doi: 10.2174/1381612054865028.
Subtypes of tetrodotoxin resistant voltage-gated sodium channels are involved in the development of certain types of neuropathic pains. After nerve injury hyperexcitability and spontaneous firing develop at the site of injury and also in the dorsal root ganglion cell bodies. This hyperexcitability results at least partly from accumulation of sodium channels at the site of injury. The facts that these sodium channels seem to exist in peripheral nerves only and that they can be blocked at the resting state (use-dependent block) offer the possibility to develop drugs, which selectively block these damaged, overexcited nerves. At the moment no such drugs are available. However, some of the most potent drugs that are currently used to manage neuropathic pain e.g. amitriptyline and other tricyclic antidepressants, also block these channels in addition to having several other mechanisms of action. Also most anticonvulsants that are used to alleviate neuropathic pain are sodium channel blockers. Lidocaine, the prototype drug, has been shown to be effective in peripheral neuropathic pain. Its use is limited by the fact that it cannot be administered orally. An oral local anesthetic type sodium channel blocker, mexiletine is an antiarrhythmic agent that is effective in neuropathic pain. However, effective doses may be difficult to achieve because of adverse effects.
对河豚毒素耐药的电压门控钠通道亚型参与了某些类型神经性疼痛的发生发展。神经损伤后，损伤部位以及背根神经节细胞体出现兴奋性过高和自发放电。这种兴奋性过高至少部分是由于损伤部位钠通道的积聚所致。这些钠通道似乎仅存在于外周神经中，并且在静息状态下可被阻断（使用依赖性阻断），这为开发选择性阻断这些受损、过度兴奋神经的药物提供了可能性。目前尚无此类药物。然而，目前用于治疗神经性疼痛的一些最有效的药物，如阿米替林和其他三环类抗抑郁药，除了具有多种其他作用机制外，也能阻断这些通道。此外，大多数用于缓解神经性疼痛的抗惊厥药都是钠通道阻滞剂。原型药物利多卡因已被证明对外周神经性疼痛有效。其使用受到不能口服给药这一事实的限制。美西律是一种口服局部麻醉型钠通道阻滞剂，是一种抗心律失常药物，对神经性疼痛有效。然而，由于不良反应，可能难以达到有效剂量。
