Pain-Modulating Peptides in Spider Venoms: Good and Evil

Abstract

While few spiders are responsible for human envenomations of medical importance, their venom contains a large variety of bio-active molecules, able to modulate neuronal ion channels and receptors. These Neurotoxins involved in the paralysis of prey and toxicity during human envenomation have been extensively studied. Some of them helped to demonstrate the role of ion channels subtypes and receptors in pain processing. In spider venoms, molecules such as biogenic amines, ATP or NGF have a role in the induction of pain. Polyamines, by blocking NMDA channels, induce prey paralysis, but some are also able to modulate TRPV1 and AMPA channels involved in pain transmission. Many peptide toxins, which share a common structure, a compact cysteine knot, activate voltage-gated sodium channels and have a synergistic action to induce pain. More recently isolated peptides have shown analgesic effects by modulating ion channels such as voltage-gated calcium channels, ASICs, P2X3, and SACs. Some of these neurotoxins could be the basis for the development of future analgesics.