第四军医大学Wang Qun研究团队近日取得一项新成果。经过不懈努力，他们揭示了5-羟色胺下降促进系统通过5-羟色胺受体参与脊髓PKCγ神经元和神经性异常性疼痛的解除抑制。相关论文发表在2025年3月16日出版的《神经科学通报》杂志上。

该研究组以不同的转基因小鼠和先进的技术为主题，揭示了下降5-羟色胺（5-HT）促进系统对脊柱PKCγ神经元的调节作用。他们的研究结果表明，来自延髓吻侧腹内侧的5-HT神经元通过5-HT2C受体使脊髓抑制性中间神经元超极化，解除了涉及pkc - γ神经元的前馈抑制回路的抑制，并加剧了异常性疼痛。抑制脊髓5-HT2C受体恢复前馈抑制回路，有效预防神经性异常性痛。这些发现为神经性异常性疼痛的治疗提供了有希望的治疗靶点，强调了脊髓5-HT2C受体作为一种新的干预途径的潜力。

据悉，神经性疼痛通常以异常性疼痛为特征，给患者带来了巨大的生理和心理负担，由于中枢机制不明确，治疗有限。解决这一挑战仍然是疼痛医学中一个关键的未解决问题。他们之前的研究，以蛋白激酶Cγ (PKCγ)-tdTomato小鼠为主题，强调了在门控神经性异常性疼痛中涉及PKCγ神经元的脊髓前馈抑制回路。然而，控制这一回路的调节机制需要进一步阐明。

附：英文原文

Title: The 5-HT Descending Facilitation System Contributes to the Disinhibition of Spinal PKCγ Neurons and Neuropathic Allodynia via 5-HT2C Receptors

Author: Zhang, Xiao, He, Xiao-Lan, Jiang, Zhen-Hua, Qi, Jing, Huang, Chen-Chen, Zhao, Jian-Shuai, Gu, Nan, Lu, Yan, Wang, Qun

Issue&Volume: 2025-03-16

Abstract: Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia. However, the regulatory mechanisms governing this circuit necessitate further elucidation. We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin (5-HT) facilitation system on spinal PKCγ neurons. Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT2C receptors, disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia. Inhibiting spinal 5-HT2C receptors restored the feedforward inhibitory circuit, effectively preventing neuropathic allodynia. These insights offer promising therapeutic targets for neuropathic allodynia management, emphasizing the potential of spinal 5-HT2C receptors as a novel avenue for intervention.

DOI: 10.1007/s12264-025-01383-7

Source: https://link.springer.com/article/10.1007/s12264-025-01383-7