Plastic change of N-type Ca channel expression after preconditioning is responsible for prostaglandin E2-induced long-lasting allodynia

Anesthesiology. 2003 Dec;99(6):1364-70. doi: 10.1097/00000542-200312000-00019.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels, N-Type / analysis
  • Calcium Channels, N-Type / physiology*
  • Carrageenan / pharmacology
  • Dinoprostone / pharmacology*
  • Dose-Response Relationship, Drug
  • Inflammation / metabolism*
  • Male
  • Pain / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • omega-Agatoxin IVA / pharmacology
  • omega-Conotoxin GVIA / pharmacology


  • Calcium Channels, N-Type
  • omega-Agatoxin IVA
  • Carrageenan
  • omega-Conotoxin GVIA
  • Dinoprostone