Du Jingyi, Deng Yifan, Qiu Zhuolin, Sun Guoliang, Guo Yue, Hei Ziqing, Li Xiang
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
J Pain Res. 2021 Apr 20;14:1061-1070. doi: 10.2147/JPR.S299604. eCollection 2021.
Cognitive impairment is a complication that most frequently happens in patients with chronic neuropathic pain and has limited effective therapy. The aim of this study was to explore the effects of curcumin on the cognitive deficit in rats with peripheral nerve injury induced-neuropathic pain.
The neuropathic pain rat model was constructed using chronic constriction injury (CCI). The curcumin (60 mg/kg) or vehicle was intraperitoneally administered once a day, beginning at 14th day after surgery and continued for 14 consecutive days. The nociceptive threshold tests were measured by paw mechanical withdraw threshold (PMWT) and paw thermal withdrawal latency (PTWL), while the spatial memory abilities were evaluated by the Morris water maze test. The mean counts of bromodeoxyuridine (Brdu)/neuronal nuclei (NeuN) as well as Brdu/doublecortin (DCX) co-labeled cells were used to evaluate neurogenesis in the dentate gyrus of hippocampus. The ultrastructure of the synapse in hippocampal region was visualized using transmission electron microscopy (TEM).
Increased PMWT and PTWL, as well as relieved memory deficits, were found in CCI rats under curcumin administration. Moreover, curcumin treatment increased the number of newly born immature (BrdU/NeuN) and newly generated mature neurons (BrdU/DCX). The TEM examination revealed increased PSD thickness and shorter active zone length as well as narrowed synaptic cleft width in the hippocampal region of CCI rats after curcumin injection.
Curcumin can alleviate CCI induced nociceptive behaviors and memory deficit. This effect might be associated with hippocampal neurogenesis and synaptic plasticity improvements, which indicated curcumin as a potential strategy for the cognitive impairment restoration under prolonged neuropathic pain condition.
认知障碍是慢性神经性疼痛患者最常出现的并发症，且有效治疗方法有限。本研究旨在探讨姜黄素对周围神经损伤诱导的神经性疼痛大鼠认知缺陷的影响。
采用慢性缩窄损伤（CCI）构建神经性疼痛大鼠模型。从术后第14天开始，每天腹腔注射一次姜黄素（60mg/kg）或溶剂，持续14天。通过 paw 机械退缩阈值（PMWT）和 paw 热退缩潜伏期（PTWL）测量伤害性阈值，同时通过 Morris 水迷宫试验评估空间记忆能力。使用溴脱氧尿苷（Brdu）/神经元细胞核（NeuN）以及 Brdu/双皮质素（DCX）共标记细胞的平均计数来评估海马齿状回中的神经发生。使用透射电子显微镜（TEM）观察海马区域突触的超微结构。
给予姜黄素的CCI大鼠的PMWT和PTWL增加，记忆缺陷得到缓解。此外，姜黄素治疗增加了新生未成熟（BrdU/NeuN）和新生成的成熟神经元（BrdU/DCX）的数量。TEM检查显示，注射姜黄素后CCI大鼠海马区域的突触后致密物（PSD）厚度增加，活性区长度缩短，突触间隙宽度变窄。
姜黄素可减轻CCI诱导的伤害性行为和记忆缺陷。这种作用可能与海马神经发生和突触可塑性改善有关，这表明姜黄素是在长期神经性疼痛状态下恢复认知障碍的潜在策略。
