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Experimental Research Article

Korean J Pain 2022; 35(4): 391-402

Published online October 1, 2022 https://doi.org/10.3344/kjp.2022.35.4.391

Copyright © The Korean Pain Society.

The role of botulinum toxin type A related axon transport in neuropathic pain induced by chronic constriction injury

Huilian Bu1 , Pengfei Jiao1,2 , Xiaochong Fan1 , Yan Gao4 , Lirong Zhang5 , Haiming Guo3

1Center of Pain Management, Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
2Zhengzhou University Academy of Medical Sciences, Zhengzhou, China
3Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, China
5School of Basic Medical Science, Zhengzhou University, Zhengzhou, China

Correspondence to:Haiming Guo
Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Longhuzhonghuan Rd., Zhengzhou 450052, China
Tel: +86-37166278936
Fax: +86-37166278936
E-mail: haiming66553@163.com

*These authors contribute equally to this work.

Handling Editor: Jong Yeon Park

Author contributions: Huilian Bu: Writing/manuscript preparation; Pengfei Jiao: Formal analysis; Xiaochong Fan: Methodology; Yan Gao: Resources; Lirong Zhang: Resources; Haiming Guo: Project administration.

Received: April 4, 2022; Revised: June 17, 2022; Accepted: June 22, 2022

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.

Keywords: Axonal Transport, Botulinum Toxins, Type A, Chemokines, Colchicine, GABA Plasma Membrane Transport Proteins, Hyperalgesia, Neuralgia, Receptors, Chemokine, Sciatic Nerve.