Brain, Vol. 125, No. 6, 1392-1401,
June 2002
© 2002 Guarantors of Brain
Adenosine A1 receptor agonists inhibit trigeminovascular nociceptive transmission
1 Headache Group, Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, 2 GlaxoSmithKline Research and Development, Stevenage, UK and 3 Department of Internal Medicine, Lund University Hospital, S-221 85 Lund, Sweden 4 Present address: Institute of Neurological Sciences, Prince of Wales Hospital, Randwick 2034, Australia
Correspondence to: Professor Peter J. Goadsby, Institute of Neurology, Queen Square, London WC1N 3BG, UK E-mail: peterg{at}ion.ucl.ac.uk
There is a considerable literature to suggest that adenosine A1 receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A1 receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (
-chloralose 60 mg/kg, intraperitoneally), and prepared for physiological monitoring. The superior sagittal sinus (SSS) was stimulated electrically, and linked units were recorded in the trigeminocervical complex. Post-stimulus histograms were constructed to analyse the responses and the effect of drug administration. Blood was sampled from the external jugular vein to determine levels of calcitonin gene-related peptide (CGRP) release before and after drug administration. Intravenous administration of the highly selective adenosine A1 receptor agonist, GR79236 (3–100 µg/kg) had a dose-dependent inhibitory effect on SSS-evoked trigeminal activity. The maximal effect (80 ± 6% reduction in probability of firing) was seen at 100 µg/kg. The neuronal inhibitory effect of GR79236 could be inhibited by the selective adenosine A1 receptor antagonist DPCPX (300 µg/kg; P < 0.05). SSS stimulation increased cranial CGRP levels from 33 ± 2 pmol/l (n = 6) to 64 ± 3 pmol/l, an effect substantially reduced by pre-treatment with GR79236 (30 µg/kg; P < 0.01). The selective low efficacy adenosine A1 receptor agonist, GR190178 (30–1000 µg/kg i.v.), also inhibited SSS-evoked neuronal activity in a dose-dependent fashion. In this model of trigeminovascular nociception, adenosine A1 receptor activation leads to neuronal inhibition without concomitant vasoconstriction, suggesting a novel avenue for the treatment of migraine and cluster headache.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. E. Benarroch Adenosine and its receptors: Multiple modulatory functions and potential therapeutic targets for neurologic disease Neurology, January 15, 2008; 70(3): 231 - 236. [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Sneyd, J. A. Langton, L. G. Allan, J. E. Peacock, and D. J. Rowbotham Multicentre evaluation of the adenosine agonist GR79236X in patients with dental pain after third molar extraction Br. J. Anaesth., May 1, 2007; 98(5): 672 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.M. A. Welch Contemporary concepts of migraine pathogenesis Neurology, October 28, 2003; 61(90084): S2 - 8. [Abstract] [Full Text]
|
|