Liu Cui-Cui, Zhang Xin-Sheng, Ruan Yu-Ting, Huang Zhu-Xi, Zhang Su-Bo, Liu Meng, Luo Hai-Jie, Wu Shao-Ling, Ma Chao
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Rehabilitation Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; and.
Zhongshan Medical School, Guangdong Province Key Laboratory of Brain Function and Disease, Sun Yat-Sen University, Guangzhou, China.
J Neurophysiol. 2017 Aug 1;118(2):1321-1328. doi: 10.1152/jn.00745.2016. Epub 2017 Jun 14.
Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia, increased MG level in plasma and dorsal root ganglion (DRG), and enhanced the excitability of small DRG neurons (<30 μm in diameter). Intrathecal injection of MG also induced mechanical allodynia, and its application to DRG neurons ex vivo increased the number of action potentials evoked by depolarizing current pulses. Furthermore, inhibition of MG accumulation by aminoguanidine attenuated the enhanced excitability of small DRG neurons and the mechanical allodynia induced by NP implantation. In addition, NP implantation increased levels of advanced glycation end products (AGEs) in DRG, and intrathecal injection of MG-derived AGEs induced the mechanical allodynia and DRG neuronal hyperactivity. Intrathecal injection of MG also significantly increased the expression of AGEs in DRG. Importantly, scavenging of MG by aminoguanidine also attenuated the increase in AGEs induced by NP implantation. These results suggested that LDH-induced MG accumulation contributed to persistent pain by increasing AGE levels. Thus generation of AGEs from MG may represent a target for treatment of LDH-induced pain. Our study demonstrates that methylglyoxal accumulation via increasing advanced glycation end-product levels in dorsal root ganglion contributes to the persistent pain induced by lumbar disk herniation, which proposed potential targets for the treatment of lumbar disk herniation-induced persistent pain.
伴有椎间盘源性下腰痛和坐骨神经痛的腰椎间盘突出症（LDH）是一种常见且复杂的肌肉骨骼疾病。其潜在机制尚不清楚，且对于LDH引起的疼痛尚无有效的治疗方法。在本研究中，我们发现患有LDH引起疼痛的患者血浆甲基乙二醛（MG）水平升高。在大鼠中，将自体髓核（NP）植入左腰5脊髓神经根以模拟LDH，可诱发机械性异常性疼痛，增加血浆和背根神经节（DRG）中的MG水平，并增强小DRG神经元（直径<30μm）的兴奋性。鞘内注射MG也可诱发机械性异常性疼痛，并且将其应用于离体DRG神经元可增加去极化电流脉冲诱发的动作电位数量。此外，氨基胍抑制MG积累可减弱小DRG神经元增强的兴奋性以及NP植入诱导的机械性异常性疼痛。另外，NP植入增加了DRG中晚期糖基化终产物（AGEs）的水平，鞘内注射MG衍生的AGEs可诱发机械性异常性疼痛和DRG神经元活动亢进。鞘内注射MG还显著增加了DRG中AGEs的表达。重要的是，氨基胍清除MG也减弱了NP植入诱导的AGEs增加。这些结果表明，LDH诱导的MG积累通过增加AGE水平导致持续性疼痛。因此，由MG生成AGEs可能是治疗LDH引起疼痛的一个靶点。我们的研究表明，通过增加背根神经节中晚期糖基化终产物水平导致的甲基乙二醛积累促成了腰椎间盘突出症引起的持续性疼痛，这为治疗腰椎间盘突出症引起的持续性疼痛提出了潜在靶点。
