Electrophysiological and transcriptomic correlates of neuropathic pain in human dorsal root ganglion neurons
Electrophysiological and transcriptomic correlates of neuropathic pain in human dorsal root ganglion neurons
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DOI：
10.1093/brain/awz063
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发表时间：
2019-05-01
期刊：
影响因子：
14.5
通讯作者：
Dougherty, Patrick M.
中科院分区：
文献类型：
--
作者：
North, Robert Y.;Li, Yan;Dougherty, Patrick M.
神经性疼痛包括多种临床实体，影响7-10%的人口，这是具有挑战性的充分治疗。在动物神经性疼痛模型的分子发现中，一些有希望的治疗方法在失败的临床试验后未能转化，这表明动物和人类之间可能存在重要的细胞水平和分子差异。通过对人体组织和/或细胞的直接研究，确定实验动物和人类之间潜在差异的程度，对于促进将临床前发现转化为有意义的治疗可能很重要。采用膜片钳电生理和rna测序对不同程度神经根性/神经性疼痛患者的背根神经节进行检测。研究结果表明，背根神经节神经元自发动作电位的产生与神经根/神经性疼痛和影像学神经根压迫有关。转录组分析表明存在性别特异性差异，并揭示了与神经根性/神经性疼痛相关的免疫反应和神经元可塑性中的基因模块和信号通路，这可能为治疗途径提供建议，并有可能在未来的队列中预测神经性疼痛。
Neuropathic pain encompasses a diverse array of clinical entities affecting 7-10% of the population, which is challenging to adequately treat. Several promising therapeutics derived from molecular discoveries in animal models of neuropathic pain have failed to translate following unsuccessful clinical trials suggesting the possibility of important cellular-level and molecular differences between animals and humans. Establishing the extent of potential differences between laboratory animals and humans, through direct study of human tissues and/or cells, is likely important in facilitating translation of preclinical discoveries to meaningful treatments. Patch-clamp electrophysiology and RNA-sequencing was performed on dorsal root ganglia taken from patients with variable presence of radicular/neuropathic pain. Findings establish that spontaneous action potential generation in dorsal root ganglion neurons is associated with radicular/neuropathic pain and radiographic nerve root compression. Transcriptome analysis suggests presence of sex-specific differences and reveals gene modules and signalling pathways in immune response and neuronal plasticity related to radicular/neuropathic pain that may suggest therapeutic avenues and that has the potential to predict neuropathic pain in future cohorts.