Sana Si Ri Gu Leng, Lv Chuanbao, Yu Shasha, Deng Xijin, Dong Yingwei
Department of Anaesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Inflammopharmacology. 2025 Jan;33(1):257-267. doi: 10.1007/s10787-024-01617-6. Epub 2024 Dec 17.
Capsaicin (CAP) induces transient pain sensation by activating transient receptor potential vanilloid-1 (TRPV1). However, the initial neuronal excitation induced by CAP is followed by a prolonged refractory period, resulting in long-lasting analgesia. Although the effects of CAP on microglia in the dorsal root ganglion of neuropathic pain disorders have been reported, the regulatory pathways of CAP on microglia remain poorly defined.
A chronic pain model was established via plantar injection of complete Freund's adjuvant (CFA), and different doses of CAP were administered to rats. Pain behavior, expression of pain-related factors, protein expression of TRPV1 in nerve cells, and the inflammatory activation of microglia were evaluated. In vitro experiments were conducted to explore the activation and migration ability of microglia, expression of inflammatory cytokines and pathway proteins, TRPV1 expression in nerve cells, and intracellular calcium concentration under different doses of CAP.
Different doses of CAP alleviated chronic pain in rats, reduced TRPV1 expression in nerve cells, and inhibited the activation of microglia; however, high doses of CAP were particularly effective in improving chronic pain. In vitro experiments confirmed that CAP reduces the secretion of inflammatory cytokines by microglia via inhibition of the TLR4/AKT/NF-κB signaling pathway. This mechanism reduced the injury and apoptosis of nerve cells, the expression of TRPV1, and the influx of calcium ions in nerve cells.
CAP reduced inflammatory responses in microglia in a dose-dependent manner by inhibiting the TLR4/AKT/NF-κB signaling pathway, which consequently reduced TRPV1 expression on neuronal cells and reduced chronic pain.
辣椒素（CAP）通过激活瞬时受体电位香草酸受体1（TRPV1）诱导短暂的痛觉。然而，CAP诱导的初始神经元兴奋之后会出现长时间的不应期，从而产生持久的镇痛作用。尽管已有报道CAP对神经性疼痛疾病背根神经节中小胶质细胞的影响，但CAP对小胶质细胞的调节途径仍不清楚。
通过足底注射完全弗氏佐剂（CFA）建立慢性疼痛模型，并给大鼠施用不同剂量的CAP。评估疼痛行为、疼痛相关因子的表达、神经细胞中TRPV1的蛋白表达以及小胶质细胞的炎性激活。进行体外实验以探究不同剂量CAP作用下小胶质细胞的激活和迁移能力、炎性细胞因子和信号通路蛋白的表达、神经细胞中TRPV1的表达以及细胞内钙浓度。
不同剂量的CAP均可减轻大鼠的慢性疼痛，降低神经细胞中TRPV1的表达，并抑制小胶质细胞的激活；然而，高剂量的CAP在改善慢性疼痛方面尤为有效。体外实验证实，CAP通过抑制TLR4/AKT/NF-κB信号通路减少小胶质细胞炎性细胞因子的分泌。该机制减少了神经细胞的损伤和凋亡、TRPV1的表达以及神经细胞中钙离子的内流。
CAP通过抑制TLR4/AKT/NF-κB信号通路以剂量依赖的方式减少小胶质细胞中的炎症反应，从而降低神经元细胞上TRPV1的表达并减轻慢性疼痛。
