Laboratory of Experimental Physiotherapy, Science of Motricity Institute, Federal University of Alfenas, Minas Gerais, Brazil.
Laboratory of Experimental Physiotherapy, Science of Motricity Institute, Federal University of Alfenas, Minas Gerais, Brazil.
Eur J Pharmacol. 2020 May 15;875:173039. doi: 10.1016/j.ejphar.2020.173039. Epub 2020 Feb 28.
Neuropathic pain is a chronic pain characterized by injury to the central or peripheral nervous system and that most often causes disability in individuals. Among the mechanisms involved in central sensitization during neuropathic pain are cytokines and chemokines released by spinal glial cells; however, these mechanisms are not well elucidated. Thus, the present study aimed to investigate the involvement of Chemokine (C-X-C motif) ligand 1 (CXCL1) and glial cells in this process. Male Wistar rats weighing 220-240 g were used and underwent a neuropathic pain model induced by chronic constriction injury (CCI). To investigate the involvement of CXCL1, chemokine receptor type 2 (CXCR2), mitogen-activated protein kinases (MAPK) p38, and microglia and astrocytes, the following drugs were used: SB225002, an CXCR2 antagonist; SML0543, a MAPK p38 inhibitor; minocycline, a microglia inhibitor; fluorocitrate, an astrocytes inhibitor; and recombinant CXCL1. The microglia, astrocytes, CXCL1, and MAPK p38 protein levels was evaluated by a Western blot assay. Furthermore, an immunofluorescence assay was performed to localize microglia and astrocytes immunoreactivity in the spinal cord. The results demonstrated that both CCI and CXCL1 induced nociception, and this effect was reversed by SB225002. In addition, minocycline, fluorocitrate, and SML0543 reversed the mechanical allodynia induced by CCI. Furthermore, there was an increase of spinal CXCL1 and microglial marker Iba1 protein levels , which was reversed by SB225002. This antagonist also reduced the Iba1 immunoreactivity in spinal cord. Thus, the present study suggests that the CXCL1 chemokine participates in neuropathic pain through CXCR2 activation in spinal microglia.
神经病理性疼痛是一种由中枢或外周神经系统损伤引起的慢性疼痛，它常导致个体残疾。在神经病理性疼痛的中枢敏化过程中涉及的机制包括由脊髓神经胶质细胞释放的细胞因子和趋化因子；然而，这些机制尚不清楚。因此，本研究旨在探讨趋化因子（C-X-C 基序）配体 1（CXCL1）和神经胶质细胞在这一过程中的作用。使用体重为 220-240g 的雄性 Wistar 大鼠，并通过慢性缩窄性损伤（CCI）建立神经病理性疼痛模型。为了研究 CXCL1、趋化因子受体 2（CXCR2）、丝裂原活化蛋白激酶（MAPK）p38 和小胶质细胞和星形胶质细胞的参与，使用了以下药物：SB225002，CXCR2 拮抗剂；SML0543，MAPK p38 抑制剂；米诺环素，小胶质细胞抑制剂；氟柠檬酸，星形胶质细胞抑制剂；和重组 CXCL1。通过 Western blot 分析评估小胶质细胞、星形胶质细胞、CXCL1 和 MAPK p38 蛋白水平。此外，还进行了免疫荧光测定以定位脊髓中小胶质细胞和星形胶质细胞的免疫反应性。结果表明，CCI 和 CXCL1 均诱导痛觉过敏，而 SB225002 逆转了这种作用。此外，米诺环素、氟柠檬酸和 SML0543 逆转了 CCI 引起的机械性痛觉过敏。此外，脊髓 CXCL1 和小胶质细胞标志物 Iba1 蛋白水平升高，SB225002 逆转了这一升高。该拮抗剂还降低了脊髓中的 Iba1 免疫反应性。因此，本研究表明 CXCL1 趋化因子通过脊髓小胶质细胞中 CXCR2 的激活参与神经病理性疼痛。
