Plastic change of N-type Ca channel expression after preconditioning is responsible for prostaglandin E-2-induced long-lasting allodynia

Background: Although considerable evidence indicates neuronal Ca channels play significant roles in pain perception, their possible importance in hypersensitization after acute inflammation has not been investigated. Methods: Using carrageenan for inducing hypersensitization, the authors investigated the analgesic effects of intrathecally administered N- and P/Q-type channel blockers, omega-conotoxin GVIA, and omega-agatoxin IVA, respectively, and also examined the level of N-type channel expression. Results. Acute inflammation, produced by carrageenan injection in a rat hind paw, caused mechanical hypersensitivity that resolved within several days. injection of prostaglandin E-2 into the same hind paw after resolution caused a markedly prolonged mechanical allodynia lasting more than 4 h. Similar but less potent prolonged allodynia was also induced in the contralateral hind paws. Intrathecal administration of omega-conotoxin GVIA (0-03-0.3 mug) produced dose-dependent inhibition of the allodynia in both control and carrageenan-preconditioned rats. However, the potency of to-conotoxin GVIA was significantly lower in carrageenan-preconditioned paws than in those in the contralateral and saline-preconditioned paws. in contrast, omega-agatoxin IVA (0.01-0.1 mug) did not reduce the allodynia. Significant up-regulation of N-type channel expression was observed in both dorsal root ganglia and the spinal cord ipsitateral to the carrageenan-preconditioned hind paw. Conclusions: The results suggest an aggravating role of the N-type channel in pain sensation and a selective plastic change of this channel expression that could underlie the mechanism of hypersensitization after acute inflammation.