Adenosine A(1) receptor agonists inhibit trigeminovascular nociceptive transmission
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/335274
- author
- Goadsby, PJ ; Hoskin, KL ; Storer, RJ ; Edvinsson, Lars LU and Connor, HE
- organization
- publishing date
- 2002
- 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
- scopus:0036014933
- 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
- 2016-04-01 12:11:53
- date last changed
- 2024-02-23 21:57:07
@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 < 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.}},
author = {{Goadsby, PJ and Hoskin, KL and Storer, RJ and Edvinsson, Lars and Connor, HE}},
issn = {{1460-2156}},
keywords = {{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}},
doi = {{10.1093/brain/awf141}},
volume = {{125}},
year = {{2002}},
}