Botulinum Toxin Type A Exerts Direct Trans-Synaptic Action at Bilateral Spinal Nociceptive Circuits.

IF 3.9 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY
Toxins Pub Date : 2025-03-14 DOI:10.3390/toxins17030140
Dalia Nemanić, Petra Šoštarić, Patrik Meglić, Ivica Matak, Lidija Bach-Rojecky
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引用次数: 0

Abstract

Botulinum toxin type A (BoNT-A) induces a bilateral analgesic effect following unilateral injection in rodent bilateral or mirror pain models. This occurs either by indirect plasticity-related actions, or by the toxin's direct central action in bilateral spinal circuits. Herein, we aimed to resolve this question by assessing the role of trans-synaptic toxin traffic in a bilateral inflammatory pain model. The analgesic effect of the toxin was examined in rats pre-treated with unilateral intraplantar BoNT-A (7 U/kg) and subsequently challenged with bilateral carrageenan-evoked hind-paw inflammation (2%, 50 µL/paw, 6 days post BoNT-A). Specific neutralizing antitoxin injected into the lumbar intrathecal space (2 IU, 24 h post BoNT-A), aimed at preventing the spinal trans-synaptic traffic of BoNT-A, abolished its bilateral analgesic effect. The toxin trans-synaptic effect was associated with reduced c-Fos neuronal activation and BoNT-A-mediated cleavage of synaptosomal-associated protein 25 (SNAP-25) in the bilateral dorsal horn. Here, we showed that, in bilaterally occurring pain, BoNT-A exerts a direct contralateral analgesic action extending beyond the level of the dorsal root ganglion sensory neuron that directly links the hindlimb injection site to the primary sensory region. This points to the crucial role of the toxin's central trans-synaptic traffic, and its direct action at propriospinal nociceptive circuits in its pain-relieving efficacy.

A型肉毒毒素在双侧脊髓伤害感觉回路中发挥直接跨突触作用。
A型肉毒毒素(BoNT-A)在啮齿类动物双侧或镜像疼痛模型中单侧注射后诱导双侧镇痛作用。这可能是通过与可塑性相关的间接作用或毒素在双侧脊髓回路中的直接中枢作用发生的。在此,我们旨在通过评估跨突触毒素运输在双侧炎症性疼痛模型中的作用来解决这个问题。以单侧足底注射BoNT-A (7 U/kg)预处理大鼠,随后以双侧卡拉胶诱发的后爪炎症(2%,50µL/只,BoNT-A后6天)刺激大鼠,研究该毒素的镇痛作用。在腰椎鞘内间隙注射特异性中和抗毒素(2 IU, BoNT-A后24 h),旨在阻止BoNT-A的脊髓跨突触运输,取消其双侧镇痛作用。毒素跨突触效应与双侧背角c-Fos神经元激活减少和bont -a介导的突触体相关蛋白25 (SNAP-25)的裂解有关。在这里,我们发现,在双侧发生的疼痛中,BoNT-A发挥直接的对侧镇痛作用,其作用范围超出了直接连接后肢注射部位和主要感觉区域的背根神经节感觉神经元的水平。这指出了毒素的中枢跨突触交通的关键作用,以及它在本体脊髓伤害感觉回路中的直接作用,以减轻疼痛的功效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Toxins
Toxins TOXICOLOGY-
CiteScore
7.50
自引率
16.70%
发文量
765
审稿时长
16.24 days
期刊介绍: Toxins (ISSN 2072-6651) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to toxins and toxinology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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