Gachon Pain Center and Department of Physiology, Gachon University College of Medicine, Incheon 21999, the Republic of Korea.
Gachon Pain Center and Department of Physiology, Gachon University College of Medicine, Incheon 21999, the Republic of Korea.
Biomed Pharmacother. 2024 Sep;178:117157. doi: 10.1016/j.biopha.2024.117157. Epub 2024 Jul 22.
Although the potent anti-inflammatory effects of irisin have been documented in various inflammatory disorders, its efficacy against inflammatory pain remains unexplored. Herein, we examined the therapeutic effects of irisin in a mouse model of inflammatory pain induced by complete Freund's adjuvant (CFA). Mice were divided into three groups: normal control, CFA-injected (CFA), and CFA plus irisin-treated (CFA+Irisin). The irisin-treated group exhibited a gradual reduction in mechanical allodynia and thermal hyperalgesia when compared with the CFA group. Moreover, treatment with irisin significantly upregulated the expression of M2 macrophage markers (interleukin [IL]-4 and IL-10) and downregulated M1 macrophage markers (IL-1β, IL-6, and tumor necrosis factor-α) in the local paw tissue, dorsal root ganglion, and spinal cord tissue. However, there was no significant difference in the total number of F4/80 macrophages in the paw tissue and dorsal root ganglion, indicating phenotypic exchange. Treatment with irisin also downregulated the expression of the glial cell activation-related markers Iba-1 and GFAP in the spinal cord tissue. To elucidate the underlying mechanisms, we detected the expression of Toll-like receptor 4 (TLR4), MyD88, and interferon regulatory factor 5 (IRF5) in paw tissues, dorsal root ganglion, and spinal tissues, revealing that irisin could downregulate the expression of these proteins. Irisin alleviated inflammatory pain by modulating local tissue inflammation and peripheral and central neuroinflammation and reducing glial cell activation and M2 macrophage polarization by modulating the TLR4-MyD88-IRF5 signaling pathway. Accordingly, irisin is a promising candidate for treating inflammatory pain in various diseases.
虽然鸢尾素在各种炎症性疾病中具有强大的抗炎作用，但它对炎症性疼痛的疗效仍未得到探索。在此，我们在完全弗氏佐剂（CFA）诱导的炎症性疼痛小鼠模型中研究了鸢尾素的治疗效果。将小鼠分为三组：正常对照组、CFA 注射组（CFA）和 CFA 加鸢尾素处理组（CFA+Irisin）。与 CFA 组相比，鸢尾素处理组的机械性痛觉过敏和热痛觉过敏逐渐减轻。此外，鸢尾素治疗显著上调了局部爪组织、背根神经节和脊髓组织中 M2 巨噬细胞标志物（白细胞介素[IL]-4 和 IL-10）的表达，并下调了 M1 巨噬细胞标志物（IL-1β、IL-6 和肿瘤坏死因子-α）。然而，爪组织和背根神经节中 F4/80 巨噬细胞的总数没有显著差异，表明表型发生了转换。鸢尾素治疗还下调了脊髓组织中胶质细胞激活相关标志物 Iba-1 和 GFAP 的表达。为了阐明潜在机制，我们检测了爪组织、背根神经节和脊髓组织中 Toll 样受体 4（TLR4）、MyD88 和干扰素调节因子 5（IRF5）的表达，结果表明鸢尾素可以下调这些蛋白的表达。鸢尾素通过调节局部组织炎症和外周及中枢神经炎症，减轻神经炎症，减少小胶质细胞激活和 M2 巨噬细胞极化，从而缓解炎症性疼痛，通过调节 TLR4-MyD88-IRF5 信号通路。因此，鸢尾素是治疗各种疾病中炎症性疼痛的有前途的候选药物。
