Bu Huilian, Jiao Pengfei, Fan Xiaochong, Gao Yan, Zhang Lirong, Guo Haiming
Center of Pain Management, Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Zhengzhou University Academy of Medical Sciences, Zhengzhou, China.
Korean J Pain. 2022 Oct 1;35(4):391-402. doi: 10.3344/kjp.2022.35.4.391.
The mechanism of peripheral axon transport in neuropathic pain is still unclear. Chemokine ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) as well as GABA transporter 1 (GAT-1) play an important role in the development of pain. The aim of this study was to explore the axonal transport of CXCL13/CXCR5 and GAT-1 with the aid of the analgesic effect of botulinum toxin type A (BTX-A) in rats.
Chronic constriction injury (CCI) rat models were established. BTX-A was administered to rats through subcutaneous injection in the hind paw. The pain behaviors in CCI rats were measured by paw withdrawal threshold and paw withdrawal latencies. The levels of CXCL13/CXCR5 and GAT-1 were measured by western blots.
The subcutaneous injection of BTX-A relieved the mechanical allodynia and heat hyperalgesia induced by CCI surgery and reversed the overexpression of CXCL13/CXCR5 and GAT-1 in the spinal cord, dorsal root ganglia (DRG), sciatic nerve, and plantar skin in CCI rats. After 10 mmol/L colchicine blocked the axon transport of sciatic nerve, the inhibitory effect of BTX-A disappeared, and the levels of CXCL13/CXCR5 and GAT-1 in the spinal cord and DRG were reduced in CCI rats.
BTX-A regulated the levels of CXCL13/CXCR5 and GAT-1 in the spine and DRG through axonal transport. Chemokines (such as CXCL13) may be transported from the injury site to the spine or DRG through axonal transport. Axon molecular transport may be a target to enhance pain management in neuropathic pain.
神经性疼痛中周围轴突运输的机制仍不清楚。趋化因子配体13(CXCL13)及其受体(C-X-C趋化因子受体5型,CXCR5)以及γ-氨基丁酸转运体1(GAT-1)在疼痛的发生发展中起重要作用。本研究旨在借助A型肉毒毒素(BTX-A)对大鼠的镇痛作用,探讨CXCL13/CXCR5和GAT-1的轴突运输情况。
建立慢性压迫损伤(CCI)大鼠模型。通过后爪皮下注射将BTX-A给予大鼠。采用爪退缩阈值和爪退缩潜伏期测量CCI大鼠的疼痛行为。通过蛋白质免疫印迹法检测CXCL13/CXCR5和GAT-1的水平。
皮下注射BTX-A可缓解CCI手术诱导的机械性异常性疼痛和热痛觉过敏,并逆转CCI大鼠脊髓、背根神经节(DRG)、坐骨神经和足底皮肤中CXCL13/CXCR5和GAT-1的过表达。10 mmol/L秋水仙碱阻断坐骨神经的轴突运输后,BTX-A的抑制作用消失,CCI大鼠脊髓和DRG中CXCL13/CXCR5和GAT-1的水平降低。
BTX-A通过轴突运输调节脊髓和DRG中CXCL13/CXCR5和GAT-1的水平。趋化因子(如CXCL13)可能通过轴突运输从损伤部位转运至脊髓或DRG。轴突分子运输可能是增强神经性疼痛疼痛管理的一个靶点。