Wolfson Institute for Biomedical Research, University College, London, UK.
Pain Med. 2011 Jul;12 Suppl 3:S93-9. doi: 10.1111/j.1526-4637.2011.01158.x.
Animal models have provided useful insights into the development and treatment of neuropathic pain. New genetic data from both human studies and transgenic mouse models suggest that specific voltage-gated sodium channel subtypes are associated with specific types of pain and, as such, may be useful analgesic drug targets for a variety of pain types including neuropathic pain. Global voltage-gated sodium channel blockers such as lidocaine have proven efficacy in treating pain but can be limited by adverse effects when administered systemically. Selective sodium channel blockers targeting channels at the periphery (Nav1.7, Nav1.8, and Nav1.9) could potentially reduce the side effect profile. Individual isoforms of voltage-gated sodium channels have been linked to particular types of pain. Nav1.7 is a useful target for ameliorating acute mechanical pain and inflammatory pain, and strong evidence also suggests that Nav1.9 could be targeted for treating inflammatory pain. Selective blockers of Nav1.8 could also have clinical benefit for visceral pain. Although there is no association between a single sodium channel isoform and neuropathic pain, combined blockade of peripherally expressed isoforms Nav1.7, Nav1.8, and Nav1.9 may prove useful.
动物模型为神经病理性疼痛的发生和治疗提供了有用的见解。来自人类研究和转基因小鼠模型的新遗传数据表明，特定的电压门控钠离子通道亚型与特定类型的疼痛相关，因此可能成为包括神经病理性疼痛在内的多种疼痛类型的有用的镇痛药物靶点。全身性应用的电压门控钠离子通道阻滞剂（如利多卡因）已被证明对疼痛治疗有效，但可能会因不良反应而受到限制。针对外周通道（Nav1.7、Nav1.8 和 Nav1.9）的选择性钠离子通道阻滞剂可能会降低副作用谱。电压门控钠离子通道的个体同工型与特定类型的疼痛有关。Nav1.7 是改善急性机械性疼痛和炎症性疼痛的有用靶点，而且也有强有力的证据表明，Nav1.9 可能成为治疗炎症性疼痛的靶点。Nav1.8 的选择性阻滞剂也可能对内脏疼痛具有临床获益。尽管没有单一的钠离子通道同工型与神经病理性疼痛相关，但外周表达的同工型 Nav1.7、Nav1.8 和 Nav1.9 的联合阻断可能会证明是有用的。
