Intrathecal administration of botulinum toxin type a antagonizes neuropathic pain by countering increased vesicular nucleotide transporter expression in the spinal cord of chronic constriction injury of the sciatic nerve rats

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM Neuropeptides Pub Date : 2023-08-01 DOI:10.1016/j.npep.2023.102346

Yongqiang Shi , Chaoyang Gong , Wei Nan , Wenming Zhou , Zeyuan Lei , Kaisheng Zhou , Linna Wang , Guanghai Zhao , Haihong Zhang

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引用次数: 1

Abstract

Botulinum toxin type A (BoNT/A) induces direct analgesic effects in neuropathic pain by inhibiting the release of substance P, calcitonin gene-related peptide (CGRP) and glutamate. Vesicular nucleotide transporter (VNUT) was responsible for the storage and release of ATP in vivo, and one of the mechanisms underlying neuropathic pain is VNUT-dependent release of extracellular ATP from dorsal horn neurons. However, the analgesic effect of BoNT/A by affecting the expression of VNUT remained largely unknown. Thus, in this study, we aimed to elucidate the antinociceptive potency and analgesic mechanism of BoNT/A in chronic constriction injury of the sciatic nerve (CCI) induced neuropathic pain. Our results showed that a single intrathecal injection of 0.1 U BoNT/A seven days after CCI surgery produced significant analgesic activity and decreased the expression of VNUT in the spinal cord of CCI rats. Similarly, BoNT/A inhibited the CCI-induced increase in ATP content in the rat spinal cord. Overexpression of VNUT in the spinal cord of CCI-induced rats markedly reversed the antinociceptive effect of BoNT/A. Furthermore, 33 U/mL BoNT/A dramatically reduced the expression of VNUT in pheochromocytoma (PC12) cells but overexpressing SNAP-25 increased VNUT expression in PC12 cells. Our current study is the first to demonstrate that BoNT/A is involved in neuropathic pain by regulating the expression of VNUT in the spinal cord in rats.

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a型肉毒毒素鞘内注射通过对抗坐骨神经慢性收缩损伤大鼠脊髓囊泡核苷酸转运蛋白表达增加而拮抗神经性疼痛

A型肉毒毒素（BoNT/A）通过抑制P物质、降钙素基因相关肽（CGRP）和谷氨酸的释放，在神经性疼痛中诱导直接镇痛作用。囊泡核苷酸转运蛋白（VNUT）负责体内ATP的储存和释放，神经性疼痛的潜在机制之一是背角神经元细胞外ATP的VNUT依赖性释放。然而，BoNT/A通过影响VNUT的表达而产生的镇痛作用在很大程度上仍然未知。因此，在本研究中，我们旨在阐明BoNT/A在坐骨神经慢性收缩损伤（CCI）诱导的神经性疼痛中的镇痛作用和镇痛机制。我们的结果表明，CCI手术后7天单次鞘内注射0.1U BoNT/a产生了显著的镇痛活性，并降低了CCI大鼠脊髓中VNUT的表达。类似地，BoNT/A抑制了CCI诱导的大鼠脊髓中ATP含量的增加。VNUT在CCI诱导的大鼠脊髓中的过表达显著逆转了BoNT/A的镇痛作用。此外，33U/mL BoNT/A显著降低了嗜铬细胞瘤（PC12）细胞中VNUT的表达，但过表达SNAP-25增加了PC12细胞中VNUT的表达。我们目前的研究首次证明BoNT/A通过调节大鼠脊髓中VNUT的表达而参与神经性疼痛。

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来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.