Cervical spondylosis may cause chronic neck pain, radiculopathy and/or myelopathy, and consequently results in severe brain damage. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for motoneurons. Accumulating microRNAs (miRNAs) have highlighted as critical regulators of GDNF signaling in the mediation of neuroinflammation and neuropathic pain. Hence, we performed this study to investigate the potential role of miR-204 in the neuropathic pain of cervical spondylotic radiculopathy (CSR) by targeting GDNF. A rat model of spinal cord compression (SCC) was established to stimulate a pathologic lesion. RT-qPCR and western blot assays characterized the downregulation of GDNF and the upregulation of miR-204 in spinal cord tissues of rats under the conditions of SCC. Moreover, miR-204 could directly target GDNF, as evidenced by dual-luciferase reporter gene assay. In order to elucidate the roles of miR-204 and GDNF in SCC-induced neuropathic pain, miR-204 sponge, GDNF, or shRNA against GDNF was introduced to the rats, followed by measurements for SCC-induced neuroinflammation and neuropathic pain. GDNF upregulation or miR-204 silencing was identified to reduce the spontaneous pain score, gait scores and cell apoptosis. Furthermore, GDNF upregulation or miR-204 silencing resulted in elevated amplitude of sensory-evoked potentials (SEPs), number of motoneurons, release of pro-inflammatory factors, TNF-α, and IL-1β in addition to an increase in the anti-inflammatory factor BDNF. Taken together, upregulation of GDNF induced by miR-204 silencing confers protection against SCC-induced pain in rat models, suggesting a potential therapeutic target for CSR treatment.

颈椎病可能导致慢性颈部疼痛、神经根病和/或脊髓病，从而导致严重的脑损伤。胶质细胞源性神经营养因子 (GDNF) 是运动神经元的有效神经营养因子。积累的 microRNA (miRNA) 已被强调为 GDNF 信号传导在神经炎症和神经性疼痛介导中的关键调节因子。因此，我们进行了这项研究，以通过靶向 GDNF 来研究 miR-204 在神经根型颈椎病 (CSR) 的神经性疼痛中的潜在作用。建立大鼠脊髓压迫（SCC）模型以刺激病理性病变。RT-qPCR 和蛋白质印迹分析表征了 SCC 条件下大鼠脊髓组织中 GDNF 的下调和 miR-204 的上调。此外，miR-204 可以直接靶向 GDNF，如双荧光素酶报告基因测定所证明的那样。为了阐明 miR-204 和 GDNF 在 SCC 诱导的神经性疼痛中的作用，将 miR-204 海绵、GDNF 或针对 GDNF 的 shRNA 引入大鼠，然后测量 SCC 诱导的神经炎症和神经性疼痛。发现 GDNF 上调或 miR-204 沉默可降低自发性疼痛评分、步态评分和细胞凋亡。此外，GDNF 上调或 miR-204 沉默导致感觉诱发电位 (SEP)、运动神经元数量、促炎因子、TNF-α 和 IL-1β 的释放以及抗-炎症因子 BDNF。总之，由 miR-204 沉默诱导的 GDNF 上调赋予大鼠模型对 SCC 诱导的疼痛的保护作用，