Department of Otolaryngological, The Affiliated Huai'an NO.1 People's Hospital of Nanjing Medical University, Huai'an Jiangsu, China.
Department of Anesthesiology, The Affiliated Huai'an NO.1 People's Hospital of Nanjing Medical University, Huai'an Jiangsu, China.
Neurochem Res. 2021 Apr;46(4):957-963. doi: 10.1007/s11064-020-03213-w. Epub 2021 Feb 10.
The complex pathogenesis and limited efficacy of available treatment make neuropathic pain difficult for long periods of time. Several findings suggested the regulatory role of microRNA in the development of neuropathic pain. This study aims to investigate the functional role of miR-122-5p in the development of neuropathic pain. Down-regulation of miR-122-5p was observed in spinal cords of rats with neuropathic pain. We also found that overexpressing miR-122-5p by intrathecal injection of miR-122-5p lentivirus in a mouse model of chronic sciatic nerve injury (CCI) prevented neuropathic pain behavior. In HEK-293 T cells, luciferase activity was significantly decreased in the transfection group with mimic-miR-122-5p in wild-type PDK4 reporter, compared with mutant PDK4 reporter. Increased PDK4 expression was also observed during the progression of neuropathic pain. Intrathecal injection of both mimic-miR-122-5p and shPDK4 in CCI mice downregulated PDK4 expression to a lower level when compared with injected with shPDK4. In CCI mice, transfection of shPDK4 suppressed mechanical allodynia and thermal hyperalgesia, while co-transfection of shPDK4 and LV-miR-122-5p resulted in stronger levels of mechanical allodynia and thermal hyperalgesia inhibition. Taken together, the data suggest that miR-122-5p inhibits PDK4 expression, attenuating neuropathic pain. This result suggests the potential role of miR-122-5p acting as a target for the treatment of neuropathic pain.
复杂的发病机制和现有治疗方法的疗效有限，使得神经病理性疼痛难以长期缓解。多项研究结果表明 microRNA 在神经病理性疼痛的发生发展中具有调控作用。本研究旨在探讨 miR-122-5p 在神经病理性疼痛发生发展中的功能作用。研究发现，神经病理性疼痛大鼠脊髓中 miR-122-5p 表达下调。我们还发现，在慢性坐骨神经损伤（CCI）小鼠模型中鞘内注射 miR-122-5p 慢病毒可上调 miR-122-5p，从而预防神经病理性疼痛行为。在 HEK-293T 细胞中，与突变型 PDK4 报告基因相比，转染 mimic-miR-122-5p 的野生型 PDK4 报告基因的荧光素酶活性显著降低。在神经病理性疼痛进展过程中也观察到 PDK4 表达增加。与鞘内注射 shPDK4 相比，CCI 小鼠鞘内注射 mimic-miR-122-5p 和 shPDK4 可将 PDK4 表达下调至更低水平。在 CCI 小鼠中，转染 shPDK4 可抑制机械性痛觉过敏和热痛觉过敏，而共转染 shPDK4 和 LV-miR-122-5p 可导致更强的机械性痛觉过敏和热痛觉过敏抑制作用。综上所述，这些数据表明 miR-122-5p 通过抑制 PDK4 表达来减轻神经病理性疼痛。这一结果表明 miR-122-5p 可能作为治疗神经病理性疼痛的靶点。
