Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science, Pilani, Rajasthan - 333 031, India.
Expert Opin Drug Discov. 2007 Feb;2(2):169-84. doi: 10.1517/17460441.2.2.169.
Neuropathic pain can be described as pain associated with damage or permanent alteration of the peripheral or central nervous system. In contrast to acute nociceptive pain, the cascade of events that arise following peripheral nerve injury leads to a maintained abnormality in the sensory system, resulting in an abnormal pain phenomenon that can be grossly debilitating. At present, there are very few effective and well-tolerated therapies for neuropathic pain. The development of animal models and constant progress in the understanding of the basic pathophysiology of neuropathic pain has led to multifarious drug targets and treatment options. The most effective agents are use-dependent inhibitors of Na(+) channels, namely phenytoin, lamotrigine and carbamazepine. Owing to an effect of increase in the serotonin and various other biogenic amine levels on the pain modulating system, various classes of antidepressants including selective serotonin re-uptake inhibitors and selective noradrenaline re-uptake inhibitors are being used clinically. Modulation of Ca(2+) channels is another useful approach for the treatment of neuropathic pain. In particular, the modulation of N-type Ca((2+)) channels, which are expressed primarily in central and peripheral nervous tissues, has been the subject of greatest interest. In view of the above, this review discusses the various strategies and approaches to novel drug discovery and pharmacotherapy of neuropathic pain syndromes.
神经病理性疼痛可被描述为与外周或中枢神经系统损伤或永久性改变相关的疼痛。与急性伤害性疼痛不同，外周神经损伤后发生的一系列事件导致感觉系统持续异常，从而产生异常的疼痛现象，可能会严重削弱身体机能。目前，针对神经病理性疼痛，有效的、耐受良好的治疗方法非常有限。动物模型的发展以及对神经病理性疼痛基础病理生理学的不断深入理解，为药物靶点和治疗选择带来了多样性。最有效的药物是钠（Na+）通道的使用依赖性抑制剂，即苯妥英、拉莫三嗪和卡马西平。由于增加 5-羟色胺和各种其他生物胺水平对疼痛调节系统的影响，包括选择性 5-羟色胺再摄取抑制剂和选择性去甲肾上腺素再摄取抑制剂在内的各类抗抑郁药在临床上得到应用。钙（Ca2+）通道的调节也是治疗神经病理性疼痛的一种有效方法。特别是对 N 型钙（Ca2+）通道的调节，该通道主要在中枢和外周神经系统组织中表达，受到了最大的关注。鉴于上述情况，本综述讨论了神经病理性疼痛综合征的新型药物发现和药物治疗的各种策略和方法。
