Plastic change of N-type Ca channel expression after preconditioning is responsible for prostaglandin E2-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 E2 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 microg) produced dose-dependent inhibition of the allodynia in both control and carrageenan-preconditioned rats. However, the potency of omega-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 microg) did not reduce the allodynia. Significant up-regulation of N-type channel expression was observed in both dorsal root ganglia and the spinal cord ipsilateral 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.
Yokoyama
Kazuaki
K
Department of Anesthesiology, Graduate School of Medicine, Tokyo Medical and Dental University, Japan.
Kurihara
Takashi
T
Makita
Koshi
K
Tanabe
Tsutomu
T
D000818:Animals; D020864:Calcium Channels, N-Type / Q000032:analysis / Q000502:physiology*; D002351:Carrageenan / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D020864:Calcium Channels, N-Type; D020867:omega-Agatoxin IVA; D002351:Carrageenan; D020866:omega-Conotoxin GVIA; D015232:Dinoprostone