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.
Highlights
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage as described by the International Association for the Study of Pain (IASP)
This review focuses on persistent pathological pain models - cancer pain and neuropathic pain (NP) because these pain states are challenging and can be effectively controlled by spider toxins
The results demonstrate that Phα1β produces analgesia after single or continuous i.t. delivery in relevant models of acute and chronic pain eliciting minimal toxic effects and with a greater therapeutic window of 16, higher than that 4 of ω-conotoxin MVIIA [15]
Summary
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage as described by the International Association for the Study of Pain (IASP) It can serve as an index of the severity and activity of a disease condition, a prognostic indicator, and a criterion of treatment efficacy [1]. Animal models of pain are extensively used to study inflammatory or pathological pain, but the use of animals possesses ethical constraints and challenges [14]. This review focuses on persistent pathological pain models - cancer pain and neuropathic pain (NP) because these pain states are challenging and can be effectively controlled by spider toxins. Phα1β (50 pmol/site) displayed significant inhibitory effects on HC-related nociception [23], demonstrating its analgesic potential in visceral pain management.
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