Effects of the calcium channel blockers Phα1β and ω-conotoxin MVIIA on capsaicin and acetic acid-induced visceral nociception in mice.

Unlabelled: The effects of intrathecal administration of the toxins Phα1β and ω-conotoxin MVIIA were investigated in visceral nociception induced by an intraperitoneal injection of acetic acid and an intracolonic application of capsaicin. The pretreatments for 2h with the toxins reduced the number of writhes or nociceptive behaviors compared with the control mice. Phα1β administration resulted in an Imax of 84±6 and an ID50 of 12 (5-27), and ω-conotoxin MVIIA resulted in an Imax of 82±9 and an ID50 of 11 (4-35) in the contortions induced by the intraperitoneal injection of acetic acid. The administration of Phα1β resulted in an Imax of 64±4 and an ID50 of 18 (9-38), and ω-conotoxin MVIIA resulted in an Imax of 71±9 and an ID50 of 9 (1-83) in the contortions induced by intracolonic capsaicin administration. Phα1β (100/site) or ω-conotoxin MVIIA (30pmol/site) pretreatments caused a reduction in CSF glutamate release in mice intraperitoneally injected with acetic acid or treated with intracolonic capsaicin. The toxin pretreatments reduced the ROS levels induced by intraperitoneal acetic acid injection. Phα1β, but not ω-conotoxin MVIIA, reduced significantly the ROS levels induced by intracolonic capsaicin administration.
Perspective: Phα1β is a ω-toxin with high therapeutic index and a broader action on calcium channels. It shows analgesic effect in several rodents' models of pain, including visceral pain, suggesting that this toxin has the potential to be used in clinical setting as a drug in the control of persistent pathological pain.
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