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

• Published in: The journal of venomous animals and toxins including tropical diseases Vol. 27
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Centro de Estudos de Venenos e Animais Peçonhentos - CEVAP, Universidade Estadual Paulista - UNESP 2021; Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP/UNESP); SciELO
• Subjects: Analgesia; CTK 01512-2; Pain; Phα1β peptide; Review; TOXICOLOGY; TROPICAL MEDICINE; TRPA1; Voltage-activated calcium channels; Analgesia; Pain; Voltage-activated calcium channels; Phα1β peptide; CTK 01512-2; TRPA1
• ISSN: 1678-9199; 1678-9199
• DOI: 10.1590/1678-9199-jvatitd-2021-0001

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.