机构：[1]Jiangsu Key Laboratory of Neuropsychiatric Diseases, Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.[2]Institute of Neuroscience, Soochow University, 199 Renai Road, Suzhou, Jiangsu, 215123, China.
Spinal muscular atrophy (SMA) is a devastating motor neuron degeneration disease caused by a deficiency of the SMN protein. Majority of patients also suffer from chronic pain. However, the pathogenesis of pain in the context of SMA has never been explored. In this study, using various pain tests, we found that a mild SMA mouse model presents with multiple forms of pain hypersensitivity. Patch-clamp recording showed that nociceptive neurons in SMA mouse dorsal root ganglia (DRGs) are hyperexcitable and their sodium current densities are markedly increased. Using quantitative RT-PCR, western blotting and immunofluorescence, we observed enhanced expression of two main voltage-gated sodium channels Na(v)1.7 and Na(v)1.8 in SMA mouse DRGs, which is at least in part due to increase in both expression and phosphorylation of NF-kappa B p50/p65 heterodimer. Moreover, we revealed that plasma norepinephrine levels are elevated in SMA mice, which contributes to mechanical hypersensitivity via the beta 2-adrenergic receptor. Finally, we uncovered that beta 2-adrenergic signaling positively modulates expression as well as phosphorylation of p50 and p65 in SMA mouse DRGs. Therefore, our data demonstrate that SMA mice, similar to humans, also develop pain hypersensitivity, and highlight a peripheral signaling cascade that elicits the mechanical sensitization in the mouse model, suggesting potential targets for therapeutic intervention.
基金：
National Natural Science Foundation of China [81530035, 81471298, 81271423]; Suzhou Clinical Research Center of Neurological Disease [Szzx201503]; Priority Academic Program Development of Jiangsu Higher Education Institutions; Jiangsu Key Laboratory of Neuropsychiatric Diseases [BM2013003]; Suzhou Science and Technology for People's Livelihood [SYS201716]
第一作者机构：[1]Jiangsu Key Laboratory of Neuropsychiatric Diseases, Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.[2]Institute of Neuroscience, Soochow University, 199 Renai Road, Suzhou, Jiangsu, 215123, China.
通讯作者：
通讯机构：[1]Jiangsu Key Laboratory of Neuropsychiatric Diseases, Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.[2]Institute of Neuroscience, Soochow University, 199 Renai Road, Suzhou, Jiangsu, 215123, China.
推荐引用方式(GB/T 7714)：
Ruobing Qu,Fuping Yao,Xiaomin Zhang,et al.SMN deficiency causes pain hypersensitivity in a mild SMA mouse model through enhancing excitability of nociceptive dorsal root ganglion neurons[J].SCIENTIFIC REPORTS.2019,9(1):6493.doi:10.1038/s41598-019-43053-5.
APA：
Ruobing Qu,Fuping Yao,Xiaomin Zhang,Yuan Gao,Tong Liu&Yimin Hua.(2019).SMN deficiency causes pain hypersensitivity in a mild SMA mouse model through enhancing excitability of nociceptive dorsal root ganglion neurons.SCIENTIFIC REPORTS,9,(1)
MLA：
Ruobing Qu,et al."SMN deficiency causes pain hypersensitivity in a mild SMA mouse model through enhancing excitability of nociceptive dorsal root ganglion neurons".SCIENTIFIC REPORTS 9..1(2019):6493
