Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China.
J Healthc Eng. 2022 Apr 6;2022:8313415. doi: 10.1155/2022/8313415. eCollection 2022.
Neuropathic pain since early diabetes swamps patients' lives, and diabetes mellitus has become an increasingly worldwide epidemic. No agent, so far, can terminate the ongoing diabetes. Therefore, strategies that delay the process and the further complications are preferred, such as diabetic neuropathic pain (DNP). Dysfunction of ion channels is generally accepted as the central mechanism of diabetic associated neuropathy, of which hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) ion channel has been verified the involvement of neuropathic pain in dorsal root ganglion (DRG) neurons. Riluzole is a benzothiazole compound with neuroprotective properties on intervention to various ion channels, including hyperpolarization-activated voltage-dependent channels. To investigate the effect of riluzole within lumbar (L3-5) DRG neurons from DNP models, streptozocin (STZ, 70 mg/kg) injection was recruited subcutaneously followed by paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL), which both show significant reduction, whilst relieved by riluzole (4 mg/kg/d) administration, which was performed once daily for 7 consecutive days for 14 days. HCN2 expression was also decreased in line with alleviated behavioral tests. Our results indicate riluzole as the alleviator to STZ-induced DNP with involvement of downregulated HCN2 in lumbar DRG by continual systemic administration in rats.
糖尿病早期就出现的神经病理性疼痛使患者苦不堪言，而糖尿病已成为一种日益流行的全球性疾病。到目前为止，还没有一种药物可以终止糖尿病的发展。因此，人们更倾向于采用能够延缓这一过程和进一步并发症的策略，比如糖尿病性神经病理性疼痛（DNP）。离子通道功能障碍通常被认为是糖尿病相关神经病变的核心机制，其中超极化激活环核苷酸门控 2（HCN2）离子通道已被证实与背根神经节（DRG）神经元的神经性疼痛有关。利鲁唑是一种苯并噻唑化合物，具有神经保护特性，可干预多种离子通道，包括超极化激活电压依赖性通道。为了研究利鲁唑对 DNP 模型中腰椎（L3-5）DRG 神经元的影响，采用链脲佐菌素（STZ，70mg/kg）皮下注射，随后进行机械性缩足反射阈值（PWMT）和热缩足潜伏期（PWTL）检测，结果均显示明显降低，而利鲁唑（4mg/kg/d）给药可缓解，给药方式为连续 7 天每天 1 次腹腔注射。HCN2 的表达也随着行为学测试的缓解而下降。我们的研究结果表明，利鲁唑通过持续的系统给药，可作为减轻 STZ 诱导的 DNP 的缓解剂，其作用机制可能涉及下调腰椎 DRG 中的 HCN2。
