Analgesic effects of Phα1β toxin: a review of mechanisms of action involving pain pathways.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2021-11-22 eCollection Date: 2021-01-01 DOI:10.1590/1678-9199-JVATITD-2021-0001

Juliana Figueira da Silva, Nancy Scardua Binda, Elizete Maria Rita Pereira, Mário Sérgio Lima de Lavor, Luciene Bruno Vieira, Alessandra Hubner de Souza, Flávia Karine Rigo, Hèlia Tenza Ferrer, Célio José de Castro, Juliano Ferreira, Marcus Vinicius Gomez

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引用次数: 5

Abstract

Phα1β is a neurotoxin purified from spider venom that acts as a high-voltage-activated (HVA) calcium channel blocker. This spider peptide has shown a high selectivity for N-type HVA calcium channels (NVACC) and an analgesic effect in several animal models of pain. Its activity was associated with a reduction in calcium transients, glutamate release, and reactive oxygen species production from the spinal cord tissue and dorsal ganglia root (DRG) in rats and mice. It has been reported that intrathecal (i.t.) administration of Phα1β to treat chronic pain reverted opioid tolerance with a safer profile than ω-conotoxin MVIIA, a highly selective NVACC blocker. Following a recent development of recombinant Phα1β (CTK 01512-2), a new molecular target, TRPA1, the structural arrangement of disulphide bridges, and an effect on glial plasticity have been identified. CTK 01512-2 reproduced the antinociceptive effects of the native toxin not only after the intrathecal but also after the intravenous administration. Herein, we review the Phα1β antinociceptive activity in the most relevant pain models and its mechanisms of action, highlighting the impact of CTK 01512-2 synthesis and its potential for multimodal analgesia.

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Phα1β毒素的镇痛作用:涉及疼痛通路的作用机制综述

Phα1β是一种从蜘蛛毒液中纯化的神经毒素，可作为高压激活（HVA）钙通道阻滞剂。这种蜘蛛肽对N型HVA钙通道（NVACC）具有高选择性，并且在几种疼痛动物模型中具有镇痛作用。其活性与大鼠和小鼠脊髓组织和背神经节根（DRG）的钙瞬变、谷氨酸释放和活性氧产生的减少有关。据报道，鞘内（i.t.）给予Phα1β治疗慢性疼痛可恢复阿片类药物耐受性，其安全性优于高选择性NVACC阻滞剂ω-conotoxin MVIIA。根据重组Phα1β（CTK 01512-2）的最新进展，已经确定了一个新的分子靶标TRPA1、二硫桥的结构排列以及对神经胶质可塑性的影响。CTK 01512-2不仅在鞘内给药后，而且在静脉给药后再现了天然毒素的抗伤害感受作用。在此，我们综述了最相关的疼痛模型中的Phα1β的镇痛活性及其作用机制，强调了CTK 01512-2合成的影响及其在多模式镇痛中的潜力。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.