Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Int J Mol Sci. 2021 Jul 1;22(13):7105. doi: 10.3390/ijms22137105.
Thymic stromal lymphopoietin (TSLP) is a well-known cytokine for T helper 2 inflammatory responses. A nerve injury activates the neuroinflammation cascade and neuron-glia interaction in dorsal root ganglions (DRG)s, leading to neuropathic pain. Therefore, this study was to investigate the role of TSLP after nerve injury. Male Sprague-Dawley rats were divided as an experimental group with chronic constriction injury (CCI) to the sciatic nerve and a control group. The mechanical pain threshold response was determined by calibration forceps. After assessment of mechanical allodynia, the ipsilateral spinal cord, DRG, sciatic nerve and skin were harvested. Immunofluorescence staining was performed to identify cell types with various markers. Western blot analyses were performed to evaluate protein expressions. Mechanical allodynia developed after CCI and persisted for the next 14 days. Astrocyte reactions occurred and continued until day 14, too. After CCI, DRG and the sciatic nerve also had significantly increased expressions of TSLP/TSLP-R/STAT5. The TSLPR was localized to sensory neuronal endings innervating the skin. This study is the first to demonstrate that the TSLP complex and the STAT5 pathway in nerve are potential therapeutic targets because of their roles in pain regulation after nerve injury.
胸腺基质淋巴细胞生成素(TSLP)是一种著名的辅助性 T 细胞 2 型炎症反应细胞因子。神经损伤会激活背根神经节(DRG)中的神经炎症级联和神经元-神经胶质相互作用,导致神经性疼痛。因此,本研究旨在探讨神经损伤后 TSLP 的作用。雄性 Sprague-Dawley 大鼠分为实验组(坐骨神经慢性缩窄性损伤)和对照组。用校准镊子测定机械痛阈反应。评估机械性痛觉过敏后,收获同侧脊髓、DRG、坐骨神经和皮肤。进行免疫荧光染色以鉴定具有各种标志物的细胞类型。进行 Western blot 分析以评估蛋白表达。CCI 后出现机械性痛觉过敏,并持续至第 14 天。星形胶质细胞反应也发生并持续到第 14 天。CCI 后,DRG 和坐骨神经中 TSLP/TSLP-R/STAT5 的表达也显著增加。TSLPR 定位于支配皮肤的感觉神经元末梢。本研究首次证明,TSLP 复合物和神经中的 STAT5 途径是潜在的治疗靶点,因为它们在神经损伤后的疼痛调节中发挥作用。