Xie Yu-Feng
Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Biomolecules. 2025 May 10;15(5):694. doi: 10.3390/biom15050694.
As a subtype of voltage-gated sodium channel and predominantly expressed in the sensory neurons located in the dorsal root ganglion (DRG), the Nav1.8 channel encoded by the gene is found to have different variants in patients suffering chronic pain or insensitivity to pain due to the gain-of-function or loss-of-function of Nav1.8 channels. In animal models of chronic pain, Nav1.8 is also verified to be involved, suggesting that Nav1.8 may be a potential target for treatment of chronic pain. Another voltage-gated sodium channel, Nav1.7, is also proposed to be a target for chronic pain, supported by clinical findings in patients and laboratory animal models; however, there is no Nav1.7-specific drug that has passed clinical trials, although they demonstrated satisfactory effects in laboratory animals. This discrepancy between clinical and preclinical studies may be related to the differences between humans and laboratory animals or due to the degeneracy in different sodium channels governing the DRG neuronal excitability, which is thought of as the underlying machinery of chronic pain and mostly studied. This review summarizes recent findings of Nav1.8 in chronic pain from clinics and laboratories and discusses the difference, which may be helpful for future investigation of Nav1.8 in chronic pain, considering the dilemma of the Nav1.7 channel in chronic pain.
作为电压门控钠通道的一种亚型，主要在背根神经节（DRG）的感觉神经元中表达，由该基因编码的Nav1.8通道在因Nav1.8通道功能获得或功能丧失而患有慢性疼痛或对疼痛不敏感的患者中发现有不同的变体。在慢性疼痛的动物模型中，Nav1.8也被证实与之相关，这表明Nav1.8可能是治疗慢性疼痛的一个潜在靶点。另一种电压门控钠通道Nav1.7也被认为是慢性疼痛的一个靶点，这得到了患者和实验动物模型的临床研究结果的支持；然而，尽管Nav1.7特异性药物在实验动物中显示出令人满意的效果，但尚无通过临床试验的此类药物。临床研究和临床前研究之间的这种差异可能与人类和实验动物之间的差异有关，或者是由于不同的钠通道在调节DRG神经元兴奋性方面的简并性，而DRG神经元兴奋性被认为是慢性疼痛的潜在机制且得到了广泛研究。这篇综述总结了临床和实验室中关于Nav1.8在慢性疼痛方面的最新研究结果，并讨论了这种差异，考虑到Nav1.7通道在慢性疼痛研究中的困境，这可能有助于未来对Nav1.8在慢性疼痛方面的研究。
