He Duan-Duan, Gao Yu, Wang Shan, Xie Zhong, Song Xue-Jun
Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
Department of Anesthesiology, Peking University International Hospital, Beijing, China.
Pain Res Manag. 2020 Feb 10;2020:3740162. doi: 10.1155/2020/3740162. eCollection 2020.
Treatment of diabetic neuropathic pain (DNP) continues to be a major challenge, and underlying mechanisms of DNP remain elusive. We investigated treatment effects of B vitamins on DPN- and DNP-associated alterations of neurochemical signaling in the nociceptive dorsal root ganglion (DRG) neurons and the spinal cord in rats.
DNP was produced in male, adult, Sprague Dawley rats by single i.p. streptozotocin (STZ). Western blot analysis and immunohistochemistry were used to analyze protein expressions in DRG and ELISA to measure the proinflammatory cytokines in the spinal cord. Behaviorally expressed DNP was determined by measuring the sensitivity of hindpaw skin to mechanical and thermal stimulation.
There were 87.5% (77/88) rats which developed high blood glucose within 1-2 weeks following STZ injection. Of which, 70.13% ( = 54/77) animals exhibited DNP manifested as mechanical allodynia and/or thermal hyperalgesia. Intraperitoneal administration of vitamins B1/B6/B12 (100/100/2 mg/kg, one or multiple doses) significantly attenuated DNP without affecting the blood glucose. Expressions of P2X3 and TRPV1 in CGRP-positive and IB4-positive DRG neurons as well as the interleukin-1, tumor necrosis factor-, and nerve growth factor in the lumbar spinal cord were greatly increased in DNP rats. Such DNP-associated neurochemical alterations were also greatly suppressed by the B-vitamin treatment.
B-vitamin treatment can greatly suppress chronic DNP and DNP-associated increased activities of P2X3 and TRPV1 in DRG and the spinal proinflammatory cytokines, which may contribute to the pathogenesis of DNP. Systematic administration of B vitamins can be a strategy for DNP management in clinic.
糖尿病性神经病理性疼痛（DNP）的治疗仍然是一项重大挑战，DNP的潜在机制仍不清楚。我们研究了B族维生素对大鼠伤害性背根神经节（DRG）神经元和脊髓中DNP及与DNP相关的神经化学信号改变的治疗效果。
通过单次腹腔注射链脲佐菌素（STZ）在成年雄性Sprague Dawley大鼠中诱导产生DNP。采用蛋白质印迹分析和免疫组织化学法分析DRG中的蛋白表达，并用酶联免疫吸附测定法检测脊髓中的促炎细胞因子。通过测量后爪皮肤对机械和热刺激的敏感性来确定行为学上表现出的DNP。
在注射STZ后的1 - 2周内，87.5%（77/88）的大鼠出现高血糖。其中，70.13%（54/77）的动物表现出DNP，表现为机械性异常性疼痛和/或热痛觉过敏。腹腔注射维生素B1/B6/B12（100/100/2 mg/kg，单剂量或多剂量）可显著减轻DNP，而不影响血糖。DNP大鼠中，CGRP阳性和IB4阳性DRG神经元中P2X3和TRPV1的表达以及腰段脊髓中白细胞介素-1、肿瘤坏死因子-α和神经生长因子的表达显著增加。B族维生素治疗也可显著抑制这些与DNP相关的神经化学改变。
B族维生素治疗可显著抑制慢性DNP以及与DNP相关的DRG中P2X3和TRPV1活性增加和脊髓促炎细胞因子增加，这可能是DNP发病机制的一部分。系统性给予B族维生素可能是临床上管理DNP的一种策略。
