Venom-based biotoxins as potential analgesics

Abstract

Chronic pain is a common debilitating condition with negative social and economic consequences. Management of chronic pain is challenging and the currently available medications do not yet yield satisfactory outcomes for many patients. Venom-derived biotoxins from various venomous species consist of several substances with different structures and compositions that include peptides. A unique characteristic of some venom-based biotoxins is the ability to block essential components of the pain signaling system, notably ion channels. This property is leading to the evaluation of the potential of biotoxins as analgesics to manage chronic pain. In addition to their therapeutic potential, biotoxins have also been essential tools to probe mechanisms underlying pain signaling, channelopathies and receptor expression. This review discusses venom-derived peptidergic biotoxins that are in preclinical stages or already in clinical trials. Some promising results from preliminary in vitro studies, ongoing challenges and unmet needs will also be discussed.

Keywords::

• analgesics
• biotoxin
• ion channels
• pain
• toxin
• venom

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Animals produced venoms that are a rich resource of biologically active substances with therapeutic potential to alleviate pain.

• Medicinal leads and some products for human use are available from venom or venom-derived substances from for example, snakes, spiders and scorpions.

• Marine creatures such as sea snails have offered a diverse range of compounds for new drugs for example, conotoxins, with one approved product (Prialt^®).

• Some venom-based biotoxins block essential components of pain signaling system, notably ion channels, but some have inhibitory effects on enzymatic activity or transmitter release.

• Effects of venom-based biotoxins on central glial cells (microglia and astrocytes) have been rarely reported and require further investigation.

• Important targets for the anti-nociceptive effects of venoms include Na_Vs, voltage-gated sodium channels, potassium channels, transient receptor potential channels, ATP receptors (e.g., P2XRs) and acid-sensing ion channels.

• A number of novel strategies (e.g., dicarba and cyclization approaches) have been employed to overcome limitations for delivery of most venom-based peptides.

• Venom-derived peptides targeting voltage-gated and ligand-gated ion channels hold promise for the advancement of our understanding of pain pathways and management of chronic pain.