神经性疼痛通常影响全球7-10%的人口,在西方国家,估计每20人中就有1人遭受社会负担。现有疗法的最大限制因素包括剂量递增问题,脱靶副作用和随机试验转化为临床实践的不良。神经性疼痛是一个广泛的术语,包括对中枢和/或外周神经系统的直接损伤/损害。导致神经元和非神经元细胞的适应不良变化,这进一步导致了自发的疼痛,感觉和运动缺陷以及对有害和非有害刺激的敏感性改变。瞬时受体电位(TRP)通道是多峰的,作为各种机械和化学刺激的生物传感器的非特异性阳离子通道,包括高渗透压,剪切应力,热,机械拉伸,胞外ATP,和其他炎症产品。这些通道的调节导致分子和细胞水平的各种生理和病理生理表现,导致包括神经性疼痛在内的疾病。在临床前研究中,有几种针对神经性疼痛的TRP通道的分子,临床试验和市场。这篇综述强调了靶向神经性疼痛的TRP通道的各种药理学调节剂的关键参与及其利用TRP通道的治疗潜力的可能结果。
Neuropathic pain generally affects 7-10% population worldwide and an estimated ∼1 in every 20 individuals in western countries suffer and burden to society. The most limiting factor with existing therapies includes dose escalation issues, off-target side effects and poor translation of randomized trials into clinical practice. Neuropathic pain is a broad term that comprises direct injury/damage to the central and/or peripheral nervous system, leads to maladaptive changes in neuronal as well as in non-neuronal cells, which further contributes to the spontaneous pain, sensory and motor deficit along with altered sensitivity towards the noxious as well as non-noxious stimulus. Transient receptor potential (TRP) channels are polymodal, non-specific cation channels that operate as biosensors to various mechanical and chemical stimuli, including hyperosmolarity, shear stress, heat, mechanical stretch, extracellular ATP, and other products of inflammation. Modulation of these channels leads to various physiological and pathophysiological manifestations at molecular and cellular levels, leading to diseases including neuropathic pain. There are several molecules targeting TRP channels for neuropathic pain in pre-clinical studies, clinical trials and in the market. This review highlights the critical involvement of various pharmacological modulators for TRP channels targeting neuropathic pain and their possible outcomes to harness the therapeutic potential of TRP channels.