Recombinant Androctonus mauretanicus mauretanicus Alpha-toxin Amm8

Alpha toxins bind voltage-independently at site-3 of sodium channels and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission . The toxin principally slows the inactivation process of TTX-sensitive sodium channels . It discriminates neuronal versus muscular sodium channel, as it is more potent on rat brain Nav1.2/SCN2A than on rat skeletal muscle Nav1.4/SCN4A . It also shows a weak activity on Nav1.7/SCN9A . In vivo, the toxin produces pain hypersensibility to mechanical and thermal stimuli.. It also exhibits potent analgesic activity, increasing hot plate and tail flick withdrawal latencies in a dose-dependent fashion . This paradoxical analgesic action, is significantly suppressed by opioid receptor antagonists, suggesting a pain-induced analgesia mechanism that involves an endogenous opioid system . This led to hypothesis that pain relief induced by peripheral administration of Amm VIII may result from sensitization of primary afferent neurons and subsequent activation of an opioid-dependent noxious inhibitory control .