Elucidating Pain Mechanism with Venom-Derived Peptides and Natural Toxins: What Doesn’t Kill You Might Treat Your Pain

Pain following envenomation is a well-known phenomenon: touching a nettle, stepping on a bee or becoming wrapped in jellyfish tentacles are relatively common encounters in our lives, and all of these have in common the memorable, and at times severe, pain that results. Indeed, pain-causing venoms and toxins have evolved on numerous occasions in many species across the animal and plant kingdoms, in particular for defensive or deterrent purposes – how else might a small insect like a bee impact a goliath like a human otherwise? Without doubt, inflicting pain is both an intuitive and evolutionarily validated strategy ensuring the survival of venomous animals, and for this reason, a plethora of venom peptides and toxins target sensory neurons. However, venom- and toxin-induced pain does not merely serve as a tool to teach us about avoidance. The at times unparalleled potency and selectivity of venom-derived peptides and natural toxins for the molecular machinery involved in the processes of signal transduction and transmission make these compounds ideally suited to unravel the mechanisms of pain. These insights in turn can be used to identify novel pain targets, or to develop potent and selective analgesic candidates.