VETINDEX

Periódicos Brasileiros em Medicina Veterinária e Zootecnia

Analgesic effects of Ph1 toxin: a review of mechanisms of action involving pain pathways

Silva, Juliana Figueira daBinda, Nancy ScarduaPereira, Elizete Maria RitaLavor, Mário Sérgio Lima deVieira, Luciene BrunoSouza, Alessandra Hubner deRigo, Flávia KarineFerrer, Hèlia TenzaCastro Júnior, Célio José deFerreira, JulianoGomez, Marcus Vinicius

Abstract Ph1 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 Ph1 to treat chronic pain reverted opioid tolerance with a safer profile than -conotoxin MVIIA, a highly selective NVACC blocker. Following a recent development of recombinant Ph1 (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 Ph1 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.

Texto completo