Department of Anesthesiology, Emergency General Hospital, Beijing, China.
Bioengineered. 2021 Dec;12(2):11390-11398. doi: 10.1080/21655979.2021.2008694.
Chronic neuroinflammation is an important factor in the development of neuropathic pain (NP). Excess microglia activation releases a mass of pro-inflammatory cytokines during neuroinflammation process, leading to a constant painful irritation of the sensory nerve. Src belongs to a non-receptor tyrosine kinase associated with sarcoma, whereas the role of Src in neuropathic pain is controversial. We designed to testify the inflammation-regulatory role of Src in the lipopolysaccharide (LPS)-induced BV2 microglia line and the mouse model of neuropathic pain by partial sciatic nerve ligation (PNL). In BV2 microglia, Src expression was inhibited using a Src family kinase inhibitor PP2 after LPS induced inflammatory response. , the neuropathic pain in mice was induced by PNL surgery and then treated with PP2. The neuroinflammation level was detected by enzyme-linked immunosorbent assay (ELISA), immunofluorescence (IF), trans-well and Western blotting (WB) assays, was examined in PNL mice using immunohistochemistry (IHC) and IF. Finally, mechanical allodynia and thermal hyperalgesia assays were used to access the functional evaluation. Inhibition of Src was decreased microglial inflammation and migration after LPS stimuli. Mechanistically, the expression of nuclear factor kappa B (NF-κB) pathway decreased after Src inhibition. The data showed that the decrease expression of Src reduced neuroinflammation and the amount of microglia in spinal dorsal horn (SDH), the mechanical allodynia of mice thereby attenuated after Src inhibition. These results indicated that the inhibition of Src took a protective effect in neuropathic pain mouse models reducing microglia-induced neuroinflammation.
慢性神经炎症是神经病理性疼痛（NP）发展的一个重要因素。小胶质细胞过度激活会在神经炎症过程中释放大量促炎细胞因子，导致感觉神经持续疼痛刺激。Src 属于与肉瘤相关的非受体酪氨酸激酶，而 Src 在神经病理性疼痛中的作用存在争议。我们旨在通过脂多糖（LPS）诱导的 BV2 小胶质细胞系和部分坐骨神经结扎（PNL）诱导的神经病理性疼痛小鼠模型来验证 Src 在炎症调节中的作用。在 LPS 诱导炎症反应后，使用 Src 家族激酶抑制剂 PP2 抑制 BV2 小胶质细胞中的 Src 表达。通过 PNL 手术诱导小鼠神经病理性疼痛，然后用 PP2 进行治疗。通过酶联免疫吸附测定（ELISA）、免疫荧光（IF）、Transwell 和 Western blot（WB）检测，用免疫组织化学（IHC）和 IF 检测 PNL 小鼠的神经炎症水平。最后，通过机械性痛觉过敏和热痛觉过敏检测来评估功能。Src 的抑制作用降低了 LPS 刺激后的小胶质细胞炎症和迁移。机制上，Src 抑制后核因子 kappa B（NF-κB）通路的表达减少。结果表明，Src 表达的减少降低了脊髓背角（SDH）中的神经炎症和小胶质细胞数量，从而减轻了 Src 抑制后的小鼠机械性痛觉过敏。这些结果表明，Src 的抑制在神经病理性疼痛小鼠模型中具有保护作用，可减轻小胶质细胞诱导的神经炎症。
