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Analgesic effects of Phα1ß toxin: a review of mechanisms of action involving pain pathways

Silva, Juliana Figueira da; Binda, Nancy Scardua; Pereira, Elizete Maria Rita; Lavor, Mário Sérgio Lima de; Vieira, Luciene Bruno; Souza, Alessandra Hubner de; Rigo, Flávia Karine; Ferrer, Hèlia Tenza; Castro Júnior, Célio José de; Ferreira, Juliano; Gomez, Marcus Vinicius.
J. venom. anim. toxins incl. trop. dis; 27: e20210001, 2021. tab, graf, ilus
Artigo em Inglês | LILACS | ID: biblio-1351017


Phα1ß 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 Phα1ß 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 Phα1ß (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 Phα1ß 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.
Biblioteca responsável: BR68.1