QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.059808v1 309/1/56    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Akerman, S. Articles by Goadsby, P. J. Search for Related Content PubMed PubMed Citation Articles by Akerman, S. Articles by Goadsby, P. J.

NEUROPHARMACOLOGY

Anandamide Is Able to Inhibit Trigeminal Neurons Using an in Vivo Model of Trigeminovascular-Mediated Nociception

Headache Group, Institute of Neurology and the National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom

Arachidonylethanolamide (anandamide, AEA) is believed to be the endogenous ligand of the cannabinoid CB₁ and CB₂ receptors. CB₁ receptors have been found localized on fibers in the spinal trigeminal tract and spinal trigeminal nucleus caudalis. Known behavioral effects of anandamide are antinociception, catalepsy, hypothermia, and depression of motor activity, similar to ⁹-tetrahydocannanbinol, the psychoactive constituent of cannabis. It may be a possible therapeutic target for migraine. In this study, we looked at the possible role of the CB₁ receptor in the trigeminovascular system, using intravital microscopy to study the effects of anandamide against various vasodilator agents. Anandamide was able to inhibit dural blood vessel dilation brought about by electrical stimulation by 50%, calcitonin gene-related peptide (CGRP) by 30%, capsaicin by 45%, and nitric oxide by 40%. CGRP_8–37 was also able to attenuate nitric oxide (NO)-induced dilation by 50%. The anandamide inhibition was reversed by the CB₁ receptor antagonist AM251. Anandamide also reduced the blood pressure changes caused by CGRP injection, this effect was not reversed by AM251. It would seem that anandamide acts both presynaptically, to prevent CGRP release from trigeminal sensory fibers, and postsynaptically to inhibit the CGRP-induced NO release in the smooth muscle of dural arteries. CB₁ receptors seem to be involved in the NO/CGRP relationship that exists in causing headache and dural blood vessel dilation. It also seems that some of the blood pressure changes caused by anandamide are mediated by a noncannabinoid receptor, as AM251 was unable to reverse these effects. It can be suggested that anandamide is tonically released to play some form of modulatory role in the trigeminovascular system.

Address correspondence to: Professor P. J. Goadsby, Institute of Neurology, Queen Square London, WC1N 3BG UK. E-mail: peterg{at}ion.ucl.ac.uk

This article has been cited by other articles:

				S. Akerman, P. R. Holland, and P. J. Goadsby Cannabinoid (CB1) Receptor Activation Inhibits Trigeminovascular Neurons J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 64 - 71. [Abstract] [Full Text] [PDF]

				P. Dinis, A. Charrua, A. Avelino, M. Yaqoob, S. Bevan, I. Nagy, and F. Cruz Anandamide-Evoked Activation of Vanilloid Receptor 1 Contributes to the Development of Bladder Hyperreflexia and Nociceptive Transmission to Spinal Dorsal Horn Neurons in Cystitis J. Neurosci., December 15, 2004; 24(50): 11253 - 11263. [Abstract] [Full Text] [PDF]