Department of Anesthesiology, Fujian Medical University Union Hospital, No. 29, Xinquan Road, Gulou District, Fuzhou 350001, Fujian, China; Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, No.34 Zhong Shan North Road, Licheng District, Quanzhou 362000, Fujian, China.
Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, No.34 Zhong Shan North Road, Licheng District, Quanzhou 362000, Fujian, China.
Brain Res Bull. 2023 Jul;199:110671. doi: 10.1016/j.brainresbull.2023.110671. Epub 2023 May 18.
BACKGROUND: Neuropathic pain is a chronic condition commonly caused by inflammation-induced disturbances or lesions of somatosensory functions in the nervous system. The aim of this study was to investigate the effects and mechanisms of Taselisib on chronic constriction injury (CCI)-induced neuropathic pain in rats. METHODS: The rats were divided into four groups: sham group, sham + Taselisib (10 mg/kg orally once a day) group, CCI group, and CCI + Taselisib (10 mg/kg orally once a day) group. Pain behavioral tests, recorded by measuring paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL), were conducted on days 0, 3, 7, 14, and 21 after surgery. After testing, the animals were euthanized and spinal dorsal horns were collected. Pro-inflammatory cytokines were quantified using ELISA and qRT-PCR. PI3K/pAKT signaling was assessed using Western blot and immunofluorescence. RESULTS: PWT and TWL were significantly reduced after CCI surgery, but were successfully increased by Taselisib treatment. Taselisib treatment notably suppressed the upregulation of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-⍺. Taselisib treatment significantly reduced the elevated phosphorylation of AKT and PI3K induced by CCI. CONCLUSION: Taselisib can alleviate neuropathic pain by inhibiting the pro-inflammatory response, potentially through the PI3K/AKT signaling pathway.
背景：神经病理性疼痛是一种慢性疾病，通常由炎症引起的感觉功能紊乱或神经系统损伤引起。本研究旨在探讨 Taselisib 对大鼠慢性缩窄性损伤（CCI）诱导的神经病理性疼痛的作用及机制。
方法：将大鼠分为 4 组：假手术组、假手术+Taselisib（10mg/kg 口服，每天 1 次）组、CCI 组和 CCI+Taselisib（10mg/kg 口服，每天 1 次）组。在手术后第 0、3、7、14 和 21 天，通过测量足底缩足反射阈值（PWT）和热缩足潜伏期（TWL）进行疼痛行为测试。测试后，处死动物并收集脊髓背角。采用 ELISA 和 qRT-PCR 定量检测促炎细胞因子。采用 Western blot 和免疫荧光法评估 PI3K/pAKT 信号通路。
结果：CCI 手术后 PWT 和 TWL 显著降低，但 Taselisib 治疗可成功升高。Taselisib 治疗显著抑制了促炎细胞因子（包括 IL-6、IL-1β和 TNF-α）的上调。Taselisib 治疗显著降低了 CCI 诱导的 AKT 和 PI3K 的磷酸化水平升高。
结论：Taselisib 通过抑制促炎反应缓解神经病理性疼痛，可能通过 PI3K/AKT 信号通路发挥作用。
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