Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, Punjab, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, Punjab, India.
Eur J Pharmacol. 2024 Oct 5;980:176845. doi: 10.1016/j.ejphar.2024.176845. Epub 2024 Jul 25.
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.
神经病理性疼痛通常影响全球 7-10%的人口，据估计，西方国家每 20 个人中就有 1 人患有这种疾病，给社会带来了负担。现有治疗方法最受限制的因素包括剂量递增问题、非靶向副作用以及随机临床试验向临床实践的转化不佳。神经病理性疼痛是一个广泛的术语，包括中枢和/或外周神经系统的直接损伤/损伤，导致神经元和非神经元细胞的适应性变化，进一步导致自发性疼痛、感觉和运动功能障碍以及对有害和非有害刺激的敏感性改变。瞬时受体电位 (TRP) 通道是多模态、非特异性阳离子通道，作为生物传感器对各种机械和化学刺激起作用，包括高渗性、切应力、热、机械拉伸、细胞外 ATP 和炎症的其他产物。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，导致包括神经病理性疼痛在内的疾病。有几种针对 TRP 通道的分子可用于治疗神经病理性疼痛，这些分子在临床前研究、临床试验和市场中都有应用。这篇综述强调了各种药理学调节剂对 TRP 通道靶向神经病理性疼痛的关键作用，以及它们可能产生的结果，以利用 TRP 通道的治疗潜力。
