杭州师范大学黄智慧小组宣布他们提出了一种新型从大细胞红核到脊髓背角的远程兴奋性神经回路促进了雄性小鼠神经性疼痛样行为。相关论文于2025年12月24日发表于国际顶尖学术期刊《神经科学通报》杂志上。

在本研究中，课题组人员发现发现大细胞红核（RMC^CaMKIIα）中的CaMKIIα阳性神经元在成年雄性小鼠腓总神经（CPN）结扎诱导的慢性神经性疼痛后被激活。有趣的是，这些RMC^CaMKIIα神经元的化学遗传和光遗传抑制减轻了神经性疼痛模型小鼠的热痛觉过敏和机械性异常性疼痛，而这些神经元的激活充分诱导了幼年小鼠的机械性异常疼痛和热痛觉过敏。跨突触病毒追踪研究进一步表明，从RMC到背角（DH）的远程CaMKIIα⁺神经元投射促进了CPN结扎后的神经性疼痛样行为。RMC^CaMKIIα神经元直接支配DH神经元，抑制RMC^CaMKIIα-DH^CaMKIIα回路可减轻结扎小鼠的神经性疼痛。综上所述，这些结果确定了一种新的从RMC到DH的远程兴奋性神经回路，促进了成年雄性小鼠的神经性疼痛样行为，为神经性疼痛治疗提供了新的靶点。

据了解，神经性疼痛源于影响体感觉系统的原发病变或疾病；然而，调控神经性疼痛的脑回路机制尚不清楚。红核（RN）是一个重要的大脑区域，参与调节肌肉张力、协调运动和促进感觉运动整合。虽然一些证据表明RN调节疼痛，但其在神经性疼痛和相关神经回路中的具体作用仍不清楚。

附：英文原文

Title: A Novel Long-range Excitatory Neural Circuit from the Magnocellular Red Nucleus to Spinal Dorsal Horn Facilitates Neuropathic Pain-like Behaviors in Male Mice

Author: Shi, Jiali, Yuan, Yinfeng, Luo, Yuhao, Guo, Yue, Lian, Jiashu, Lin, Lin, Chen, Danni, Wang, Qian, Xue, Xiumin, Chen, Zhichao, Wang, Yongjie, Huang, Zhihui

Issue&Volume: 2025-12-24

Abstract: Neuropathic pain arises from a primary lesion or disease affecting the somatosensory system; however, the brain circuitry underlying the regulation of neuropathic pain remains unclear. The red nucleus (RN) is a critical brain region involved in regulating muscle tension, coordinating movement, and facilitating sensorimotor integration. While some evidence has shown that RN regulates pain, its specific role in neuropathic pain and associated neural circuits remains elusive. In this study, we found that CaMKIIα-positive neurons in the magnocellular red nucleus (RMCCaMKIIα) were activated following common peroneal nerve (CPN) ligation-induced chronic neuropathic pain in adult male mice. Interestingly, chemogenetic and optogenetic inhibition of these RMCCaMKIIα neurons alleviated the thermal hyperalgesia and mechanical allodynia in the neuropathic pain model mice, whereas activation of these neurons sufficiently induced the mechanical allodynia and thermal hyperalgesia in nave mice. Trans-synaptic viral tracing studies further revealed that long-range CaMKIIα+ neuron projections from RMC to the dorsal horn (DH) facilitated the neuropathic pain-like behaviors following CPN ligation. DH neurons received direct innervation from RMCCaMKIIα neurons, and inhibition of RMCCaMKIIα-DHCaMKIIα circuits alleviated the neuropathic pain in the ligated mice. Taken together, these results identify a novel long-range excitatory neural circuit from RMC to DH that facilitates the neuropathic pain-like behaviors in adult male mice, providing a new target for neuropathic pain treatment.

DOI: 10.1007/s12264-025-01553-7

Source: https://link.springer.com/article/10.1007/s12264-025-01553-7