Department of Pain Medicine, The Affiliated People's Hospital of Jiangsu University, Jiangsu 212000, China.
Department of Pain Medicine, The Affiliated People's Hospital of Jiangsu University, Jiangsu 212000, China.
Neurosci Lett. 2023 Sep 14;813:137429. doi: 10.1016/j.neulet.2023.137429. Epub 2023 Aug 11.
Neuropathic pain refers to a type of pain that arises from primary damage and dysfunction within the nervous system. Addressing this condition presents significant challenges and complexities. Betulinic acid (BA), known for its potent antioxidative and anti-inflammatory properties, has garnered extensive attention; nevertheless, the impact upon neuropathic pain induced by CCI is still uncertain. This paper explores the analgesic effects concerning BA on mice experiencing neuropathic pain due to sciatic nerve injury. Throughout the experiment, mice with CCI received oral gavage of BA at dosages of 3, 10, and 30 mg/kg for consecutively 8 days from the 7th day post-surgery. To assess their responses, behavioral tests and sciatic functional index (SFI) evaluations were conducted on zeroth, seventh, eighth, tenth, twelveth and fourteenth day post-CCI. On day 14, histopathological examinations and measurements of biochemical markers were performed. Immunofluorescence techniques were employed to detect Nrf2 and glial cell activation, while the Western blot method was utilized to evaluate Nrf2/HO-1 protein levels and pro-inflammatory cytokine expression. The results elucidated that BA significantly alleviated hyperalgesia and allodynia, demonstrating a dose-dependent enhancement in sciatic nerve function and facilitating the recovery of sciatic nerve injury. Furthermore, BA prominently augmented the entire antioxidative capacity (T-AOC) and T-SOD levels, concomitantly reducing MDA concentrations. Notably, BA activated the Nrf2/HO-1 signaling pathway, inhibited glial cell activation, and downregulation of the expression levels of pro-inflammatory cytokines, specifically, TNF-α, IL-1β, and IL-6 were observed. As such, this study provides a basis to support BA as a candidate drug for the treatment of neuropathic pain, attributing its analgesic effects to its anti-inflammatory, antioxidative, and neuroprotective properties.
神经病理性疼痛是指一种源自神经系统原发性损伤和功能障碍的疼痛。这种病症的治疗极具挑战性和复杂性。白桦脂酸（BA）因其强大的抗氧化和抗炎特性而备受关注；然而，其对CCI 诱导的神经病理性疼痛的影响尚不确定。本文探讨了白桦脂酸（BA）对坐骨神经损伤所致神经病理性疼痛小鼠的镇痛作用。在整个实验过程中，CCI 后的第 7 天开始，连续 8 天，每天对小鼠进行 3、10 和 30mg/kg 的口服灌胃，以评估其反应。在第 0、7、8、10、12 和 14 天对 CCI 后进行行为测试和坐骨神经功能指数（SFI）评估。第 14 天进行组织病理学检查和生化标志物测量。采用免疫荧光技术检测 Nrf2 和神经胶质细胞激活，Western blot 方法评估 Nrf2/HO-1 蛋白水平和促炎细胞因子表达。结果表明，BA 显著缓解了痛觉过敏和触诱发痛，表现出剂量依赖性的坐骨神经功能增强，并促进了坐骨神经损伤的恢复。此外，BA 明显增加了总抗氧化能力（T-AOC）和 T-SOD 水平，同时降低了 MDA 浓度。值得注意的是，BA 激活了 Nrf2/HO-1 信号通路，抑制了神经胶质细胞的激活，下调了促炎细胞因子的表达水平，具体来说，TNF-α、IL-1β 和 IL-6 的表达水平降低。因此，这项研究为支持 BA 作为治疗神经病理性疼痛的候选药物提供了依据，其镇痛作用归因于其抗炎、抗氧化和神经保护特性。
