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

Juliana Figueira da Silva1, Nancy Scardua Binda1, Elizete Maria Rita Pereira2, Mário Sérgio Lima de Lavor3, Luciene Bruno Vieira4, Alessandra Hubner de Souza2, Flávia Karine Rigo5, Hèlia Tenza Ferrer6, Célio José de Castro Júnior2, Juliano Ferreira7, Marcus Vinicius Gomez2,6 [ + show more ]

J Venom Anim Toxins incl Trop Dis, 2021, 27:e20210001
Received: 03 January 2021 | Accepted: 26 March 2021 | Published online: 22 November 2021
Collection: Arthropods: venoms and biology


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.


Keywords: Pain; Analgesia; Phα1β peptide; CTK 01512-2; Voltage-activated calcium channels; TRPA1.

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