Neuroscience and Pain Research Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Department of Anaesthesiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Life Sci. 2022 Jan 1;288:120187. doi: 10.1016/j.lfs.2021.120187. Epub 2021 Nov 30.
Chemotherapy-induced neuropathic pain (CINP) is among the most common clinical complications associated with the use of anti-cancer drugs. CINP occurs in nearly 68.1% of the cancer patients receiving chemotherapeutic drugs. Most of the clinically available analgesics are ineffective in the case of CINP patients as the pathological mechanisms involved with different chemotherapeutic drugs are distinct from each other. CINP triggers the somatosensory nervous system, increases the neuronal firing and activation of nociceptive mediators including transient receptor protein vanilloid 1 (TRPV1). TRPV1 is widely present in the peripheral nociceptive nerve cells and it has been reported that the higher expression of TRPV1 in DRGs serves a critical role in the potentiation of CINP. The therapeutic glory of TRPV1 is well recognized in clinics which gives a promising insight into the treatment of pain. But the adverse effects associated with some of the antagonists directed the scientists towards RNA interference (RNAi), a tool to silence gene expression. Thus, ongoing research is focused on developing small interfering RNA (siRNA)-based therapeutics targeting TRPV1. In this review, we have discussed the involvement of TRPV1 in the nociceptive signaling associated with CINP and targeting this nociceptor, using siRNA will potentially arm us with effective therapeutic interventions for the clinical management of CINP.
化疗诱导性神经痛（CINP）是与抗癌药物使用相关的最常见临床并发症之一。接受化疗药物治疗的癌症患者中，近 68.1%会发生 CINP。由于涉及不同化疗药物的病理机制彼此不同，大多数临床可用的镇痛药在 CINP 患者中无效。CINP 会触发躯体感觉神经系统，增加神经元的发射和伤害性介质（包括瞬时受体蛋白香草素 1（TRPV1））的激活。TRPV1 广泛存在于周围伤害性神经细胞中，据报道，DRGs 中 TRPV1 的高表达在增强 CINP 中起着关键作用。TRPV1 在临床上的治疗效果已得到广泛认可，这为疼痛治疗提供了有希望的思路。但一些针对 TRPV1 的拮抗剂的不良反应促使科学家转向 RNA 干扰（RNAi），这是一种沉默基因表达的工具。因此，目前的研究重点是开发针对 TRPV1 的基于小干扰 RNA（siRNA）的治疗方法。在这篇综述中，我们讨论了 TRPV1 在与 CINP 相关的伤害性信号转导中的作用，并讨论了使用 siRNA 靶向这个伤害感受器，这可能为我们提供有效的治疗干预措施，用于 CINP 的临床管理。
