Zhang Xiaofei, Li Xiaohui, Wang Huan, Xie Xianqiao, Li Yang, Xu Xueqin, Su Shanchun, Zhao Haiwen, Li Junhong, Ke Changbin, Liu Juying
Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Neurosci Res. 2021 May;166:34-41. doi: 10.1016/j.neures.2020.05.010. Epub 2020 May 23.
Neuropathic pain is a very complex chronic pain state, the detailed molecular mechanisms of which remain unclear. In the present study, Shank3 was found to play an important role in neuropathic pain in rats following spared nerve injury (SNI). Shank3 was upregulated in the spinal dorsal horn of rats subjected to SNI, and mechanical hypersensitivity to noxious stimuli in these rats could be alleviated by knock down of Shank3. Shank3 also interacted with hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) and promoted the expression of HCN2 in central neurons of the spinal dorsal. Together with the SNI-dependent increase of HCN2, we also found that the postsynaptic protein of excitatory synapse (PSD95) was increased in rats following SNI. Taken together, our results showed that Shank3 modulated neuropathic pain by facilitating the SNI-dependent increase of HCN2 and the expression of PSD95 in spinal dorsal horn neurons. Our findings revealed new synaptic remodeling mechanisms linking Shank3 with neuropathic pain.
神经性疼痛是一种非常复杂的慢性疼痛状态，其详细的分子机制仍不清楚。在本研究中，发现Shank3在 spared nerve injury (SNI) 后的大鼠神经性疼痛中起重要作用。在遭受SNI的大鼠脊髓背角中，Shank3表达上调，敲低Shank3可减轻这些大鼠对有害刺激的机械性超敏反应。Shank3还与超极化激活的环核苷酸门控通道2 (HCN2) 相互作用，并促进脊髓背侧中枢神经元中HCN2的表达。连同SNI依赖的HCN2增加，我们还发现SNI后大鼠兴奋性突触的突触后蛋白 (PSD95) 增加。综上所述，我们的结果表明，Shank3通过促进脊髓背角神经元中SNI依赖的HCN2增加和PSD95的表达来调节神经性疼痛。我们的发现揭示了将Shank3与神经性疼痛联系起来的新的突触重塑机制。
