Analgesic effect in rodents of native and recombinant Phα1β toxin, a high-voltage-activated calcium channel blocker isolated from armed spider venom

Calcium influx through neuronal voltage-sensitive calcium channels (VSCCS) mediates nociceptive information in the spinal dorsal horn. In fact, spinally administered VSCCS blockers, such as ω-conotoxin MVIIA, have analgesic effect apart of their low therapeutic index and many side effects. Here we study the analgesic potential of Phα1β, a calcium channel blocker, in rodent models of acute and persistent pain. Spinally administered Phα1β showed higher efficacy and long-lasting analgesia in a thermal model of pain, when compared with ω-conotoxin MVIIA. Moreover, Phα1β was more effective and potent than ω-conotoxin MVIIA not only to prevent, but especially to reverse, previously installed persistent chemical and neuropathic pain. Furthermore, the analgesic action of both toxins are related with the inhibition of Ca2+-evoked release of pro-nociceptive neurotransmitter, glutamate, from rat spinal cord synaptosomes and decrease of glutamate overflow in cerebrospinal fluid. When side effects were assessed, we found that Phα1β had a therapeutic index wider than ω- conotoxin MVIIA. Finally, recombinant Phα1β expressed in Escherichia coli showed marked analgesic activity similar to the native toxin. Taken together, the present study demonstrates that native and recombinant Phα1β have analgesic effects in rodent models of pain, suggesting that this toxin may have potential to be used as a drug in the control of persistent pathological pain.