Kouroki Satoshi, Maruta Toyoaki, Hidaka Kotaro, Koshida Tomohiro, Kurogi Mio, Kage Yohko, Miura Ayako, Nakagawa Hikaru, Yanagita Toshihiko, Takeya Ryu, Tsuneyoshi Isao
Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Miyazaki, Japan.
Department of Pharmacology, Faculty of Medicine, University of Miyazaki, Miyazaki, Miyazaki, Japan.
PLoS One. 2025 May 30;20(5):e0323628. doi: 10.1371/journal.pone.0323628. eCollection 2025.
Neuropathic pain has a significant social impact, with high morbidity and reduced productivity, the underlying mechanisms of neuropathic pain remain poorly understood, and effective therapeutic strategies remain elusive. The development of animal models of neuropathic pain that stimulate only the nociceptors and not the other sensory receptors or motor nerves is desirable for elucidating the complex pathogenesis of neuropathic pain. We have previously reported the generation of NaV1.7-channelrhodopsin-2 (ChR2), NaV1.8-ChR2, and NaV1.9-ChR2 mice. Optogenetics was employed in these light-responsive pain mice for generating nociceptive pain by specifically exciting the spinal dorsal root ganglion neurons, in which the respective Na+ channels are expressed through exposure to blue light. This study aimed to compare the neuropathic pain produced by the prolonged exposure of light-responsive pain mice to blue light. A reversible neuropathic pain state was established persisting for a minimum of 24 hours when each light-responsive pain mouse was irradiated with light of an intensity that consistently elicited pain. Furthermore, the mice also showed pain sensitivity to light irradiation and mechanical stimulation. The expression of c-Fos, a marker for neuronal activity following noxious stimulation, was increased in the dorsal horn of the spinal cord on the light irradiated side. DS-1971a, a selective NaV1.7 inhibitor, was effective in attenuating neuropathic pain in all light-responsive pain mice. In conclusion, optogenetics helps elucidate the specific functions of sodium channel subtypes in pain signaling, thereby advancing our understanding and paving the way for the development of further effective treatments for pain disorders in the future.
神经性疼痛具有重大的社会影响，发病率高且生产力下降，但其潜在机制仍知之甚少，有效的治疗策略也难以捉摸。开发仅刺激伤害感受器而不刺激其他感觉感受器或运动神经的神经性疼痛动物模型，对于阐明神经性疼痛的复杂发病机制是很有必要的。我们之前报道过生成Nav1.7-通道视紫红质-2（ChR2）、Nav1.8-ChR2和Nav1.9-ChR2小鼠。在这些光反应性疼痛小鼠中采用光遗传学方法，通过特异性地激发脊髓背根神经节神经元来产生伤害性疼痛，其中各自的Na+通道通过暴露于蓝光而表达。本研究旨在比较光反应性疼痛小鼠长时间暴露于蓝光所产生的神经性疼痛。当用持续引发疼痛的强度的光照射每只光反应性疼痛小鼠时，建立了一种持续至少24小时的可逆性神经性疼痛状态。此外，小鼠对光照射和机械刺激也表现出疼痛敏感性。c-Fos是伤害性刺激后神经元活动的标志物，其表达在光照射侧脊髓背角中增加。DS-1971a是一种选择性Nav1.7抑制剂，对减轻所有光反应性疼痛小鼠的神经性疼痛有效。总之，光遗传学有助于阐明钠通道亚型在疼痛信号传导中的特定功能，从而增进我们的理解，并为未来开发更有效的疼痛疾病治疗方法铺平道路。
