Ossipov Michael H, Porreca Frank
Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona 85724, USA.
NeuroRx. 2005 Oct;2(4):650-61. doi: 10.1602/neurorx.2.4.650.
Neuropathic pain might best be considered as a collection of various pain states with a common feature, that being symptoms suggestive of dysfunction of peripheral nerves. The development of therapeutic options for the treatment of neuropathic pain is complicated significantly by several factors. Neuropathic pain may arise from widely diverse etiologies such as physical trauma, disease, infection, or chemotherapy. Symptoms indicative of neuropathic pain may also arise in individuals with no evidence of any type of nerve trauma (idiopathic). Although neuropathic pain is a substantial health care issue, it is relatively uncommon and only occurs in a small fraction (<10%) of individuals with these initiating factors. Moreover, the efficacy of treatment protocols, even against the same type of symptoms, differ depending on the underlying initiating cause of the neuropathy. Although these observations strongly suggest that there are predisposing factors that may impart susceptibility to the development of neuropathic pain, no common predisposing factors or genetic markers have been satisfactorily identified. Because of these vagaries, treatment of neuropathic pain has been based on trial and error. However, recent progress in the understanding of neurophysiologic changes that accompany peripheral nerve dysfunction indicate that regulation of ion channels that maintain membrane potentials or generate action potentials may provide an important therapeutic approach. Neuropathic pain is accompanied by increased activity of peripheral nociceptors, which is produced in part by changes in levels of specific calcium and sodium channels. The identification of sodium and/or calcium channels subtypes that are expressed almost exclusively on nociceptors may provide a way of regulating the activity of exaggerated nociceptor function without altering other sensory modalities. Thus, the selective targeting of ion channels may represent a viable therapeutic target for the management of the neuropathic pain state, regardless of etiology.
神经病理性疼痛或许最好被视为一系列具有共同特征的不同疼痛状态，即存在提示周围神经功能障碍的症状。多种因素显著地使神经病理性疼痛治疗方案的开发变得复杂。神经病理性疼痛可能源于广泛多样的病因，如身体创伤、疾病、感染或化疗。在没有任何类型神经创伤证据（特发性）的个体中，也可能出现提示神经病理性疼痛的症状。尽管神经病理性疼痛是一个重大的医疗保健问题，但它相对不常见，仅在有这些起始因素的一小部分（<10%）个体中发生。此外，即使针对相同类型的症状，治疗方案的疗效也因神经病变的潜在起始原因而异。尽管这些观察结果强烈表明存在可能使个体易患神经病理性疼痛的易感因素，但尚未令人满意地确定常见的易感因素或基因标记。由于存在这些变幻莫测的情况，神经病理性疼痛的治疗一直基于反复试验。然而，最近在理解伴随周围神经功能障碍的神经生理变化方面取得的进展表明，调节维持膜电位或产生动作电位的离子通道可能提供一种重要的治疗方法。神经病理性疼痛伴随着外周伤害感受器活性的增加，这部分是由特定钙通道和钠通道水平的变化所导致的。鉴定几乎仅在伤害感受器上表达的钠通道和/或钙通道亚型，可能提供一种在不改变其他感觉模式的情况下调节过度的伤害感受器功能活性的方法。因此，无论病因如何，选择性靶向离子通道可能是管理神经病理性疼痛状态的一个可行治疗靶点。
