Exploiting animal toxins to probe molecular mechanisms of pain

Venoms from spiders, snakes, cone snails and scorpions have evolved to produce avast pharmacopoeia of toxins that modulate receptor or channel function as a means ofproducing shock, hemolysis, paralysis and pain. As such, venoms from these animalsrepresent a rich potential source of potent and selective toxins that can be exploited tostudy and manipulate somatosensory and nociceptive signaling pathways. In this work, Ihave identified and characterized two novel toxins from the Brazilian lancehead pit viper(Bothrops moojeni) and Tanzania blue ringleg centipede (Scolopendra morsitans). TheBrazilian lancehead snake venom contains a novel secreted phospholipase A2(sPLA2)-like protein that can promote ATP release from pannexin hemichannels.Studies on the cellular and behavioral effects of this toxin reveal a role of regulatedendogenous nucleotide release in nociception. The discovered Tanzania blue ringlegcentipede toxin represents a new family of toxins that show evolutionary relationshipwith α-scorpion toxins and could potentially function as potassium channel blockers