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Adenosine A(1) receptor agonists inhibit trigeminovascular nociceptive transmission

Goadsby, PJ; Hoskin, KL; Storer, RJ; Edvinsson, Lars LU and Connor, HE (2002) In Brain 125. p.1392-1401
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.... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
migraine, headache, adenosine A(1) receptor agonist, pain, cat, GR79236, GR190178
in
Brain
volume
125
pages
1392 - 1401
publisher
Oxford University Press
external identifiers
  • pmid:12023327
  • wos:000176282700020
ISSN
1460-2156
DOI
10.1093/brain/awf141
language
English
LU publication?
yes
id
01f8604e-d060-46c7-87fe-ba15c60e256e (old id 335274)
date added to LUP
2007-08-20 16:38:32
date last changed
2016-04-15 19:55:05
@article{01f8604e-d060-46c7-87fe-ba15c60e256e,
  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 &lt; 0.05). SSS stimulation increased cranial CGRP levels from 33 &amp;PLUSMN; 2 pmol/l (n = 6) to 64 &amp;PLUSMN; 3 pmoll, an effect substantially reduced by pre-treatment with GR79236 (30 μg/kg; P &lt; 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.},
  author       = {Goadsby, PJ and Hoskin, KL and Storer, RJ and Edvinsson, Lars and Connor, HE},
  issn         = {1460-2156},
  keyword      = {migraine,headache,adenosine A(1) receptor agonist,pain,cat,GR79236,GR190178},
  language     = {eng},
  pages        = {1392--1401},
  publisher    = {Oxford University Press},
  series       = {Brain},
  title        = {Adenosine A(1) receptor agonists inhibit trigeminovascular nociceptive transmission},
  url          = {http://dx.doi.org/10.1093/brain/awf141},
  volume       = {125},
  year         = {2002},
}