Upadhyay Aman, Gradwell Mark A, Vajtay Thomas J, Conner James, Sanyal Arnab A, Azadegan Chloe, Patel Komal R, Thackray Joshua K, Bohic Manon, Imai Fumiyasu, Ogundare Simon O, Yoshida Yutaka, Abdus-Saboor Ishmail, Azim Eiman, Abraira Victoria E
W.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA; Department of Cell Biology and Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA; Brain Health Institute, Rutgers University, Piscataway, NJ, USA; Graduate Program in Neuroscience, Rutgers Robert Wood Johnson Medical School, Rutgers University, The State University of New Jersey, Piscataway, NJ, USA.
W.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA; Department of Cell Biology and Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA; Brain Health Institute, Rutgers University, Piscataway, NJ, USA.
Cell Rep. 2025 Apr 22;44(4):115556. doi: 10.1016/j.celrep.2025.115556. Epub 2025 Apr 8.
During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading to the perception of touch as pain, known as mechanical allodynia. The brain stem dorsal column nuclei integrate tactile inputs, yet their role in mediating tactile sensitivity and allodynia remains understudied. We found that gracile nucleus (Gr) inhibitory interneurons and thalamus-projecting neurons are differentially innervated by primary afferents and spinal inputs. Functional manipulations of these distinct Gr neuronal populations bidirectionally shifted tactile sensitivity but did not affect noxious mechanical or thermal sensitivity. During neuropathic pain, Gr neurons exhibited increased sensory-evoked activity and asynchronous excitatory drive from primary afferents. Silencing Gr projection neurons or activating Gr inhibitory neurons in neuropathic mice reduced tactile hypersensitivity, and enhancing inhibition ameliorated paw-withdrawal signatures of neuropathic pain and induced conditioned place preference. These results suggest that Gr activity contributes to tactile sensitivity and affective, pain-associated phenotypes of mechanical allodynia.
在病理状态下，触觉刺激可异常激活伤害性感受通路，导致将触觉感知为疼痛，即所谓的机械性异常性疼痛。脑干背柱核整合触觉输入，但其在介导触觉敏感性和异常性疼痛中的作用仍未得到充分研究。我们发现，薄束核（Gr）抑制性中间神经元和投射到丘脑的神经元受初级传入纤维和脊髓输入的支配方式不同。对这些不同的Gr神经元群体进行功能操作可双向改变触觉敏感性，但不影响有害机械或热敏感性。在神经性疼痛期间，Gr神经元表现出感觉诱发活动增加以及来自初级传入纤维的异步兴奋性驱动。在神经性小鼠中沉默Gr投射神经元或激活Gr抑制性神经元可降低触觉超敏反应，增强抑制作用可改善神经性疼痛的爪退缩特征并诱导条件性位置偏爱。这些结果表明，Gr的活动有助于触觉敏感性以及机械性异常性疼痛的情感性、与疼痛相关的表型。
