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Sökning: WFRF:(Goadsby PJ)

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  • Goadsby, PJ, et al. (författare)
  • Adenosine A(1) receptor agonists inhibit trigeminovascular nociceptive transmission
  • 2002
  • Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 125, s. 1392-1401
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a considerable literature to suggest that adenosine A(1) receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A(1) receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (alpha-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 A(1) receptor agonist, GR79236 (3-100 mug/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 mug/kg. The neuronal inhibitory effect of GR79236 could be inhibited by the selective adenosine A(1) receptor antagonist DPCPX (300 mug/kg; P < 0.05). SSS stimulation increased cranial CGRP levels from 33 &PLUSMN; 2 pmol/l (n = 6) to 64 &PLUSMN; 3 pmoll, an effect substantially reduced by pre-treatment with GR79236 (30 μg/kg; P < 0.01). The selective low efficacy adenosine A(1) receptor agonist, GR190178 (30-1000 mug/kg i.v.), also inhibited SSS-evoked neuronal activity in a dose-dependent fashion. In this model of trigeminovascular nociception, adenosine A(1) receptor activation leads to neuronal inhibition without concomitant vasoconstriction, suggesting a novel avenue for the treatment of migraine and cluster headache.
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