TRPV1 receptor blockade is ineffective in different in vivo models of migraine.
BACKGROUND
It has been proposed that TRPV1 receptors may play a role modulating trigeminal sensory processing. We used models of trigeminovascular nociceptive activation to study the involvement of TRPV1 receptors in the rat. Due to a possible role of TRPV1 receptors in cortical spreading depression (CSD), an experimental phenomenon sharing many features with migraine aura, we also utilized a model of mechanically induced CSD.


METHODS
Male Sprague Dawley rats (N = 39) were anesthetized and cannulated for monitoring and drug administration to study the effects of the TRPV1 receptor antagonist A-993610 (8 mg kg(-1) IV). Wide-dynamic-range neurons, responding to electrical stimulation of the middle meningeal artery (MMA)/dura mater were identified and recorded using electrophysiological techniques. Intravital microscopy was used to study neurogenic dural vasodilation (NDV) of the MMA comparing capsaicin and electrical stimulation, and the effect of A-993610 on mechanically induced CSD was examined.


RESULTS
Administration of A-993610 had no significant effect on trigeminal firing of A- or C-fibers elicited by electrical stimulation of the MMA. It also showed no effect on NDV whilst blocking vasodilation due to intravenous capsaicin injection. The mechanically induced CSD response could not be altered by A-993610 administration.


CONCLUSIONS
Although there is evidence that TRPV1 receptors play an important role in sensory processing in general, the new data do not support a role in the treatment of acute migraine.
Summ
Oliver
O
University of California, USA.
Holland
Philip R
PR
Akerman
Simon
S
Goadsby
Peter J
PJ
D000208:Acute Disease; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D013181:Cortical Spreading Depression / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D020325:Migraine with Aura / Q000188:drug therapy*; D016602:Needlestick Injuries; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D014276:Trigeminal Nerve / Q000187:drug effects*; D061221:Trigeminal Nerve Injuries; D014664:Vasodilation / Q000187:drug effects*
D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D002211:Capsaicin