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The roles of spinal adenosine receptors in the control of acute and more persistent nociceptive responses of dorsal horn neurones in the anaesthetized rat
Author(s) -
Reeve Alison J.,
Dickenson Anthony H.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15057.x
Subject(s) - agonist , adenosine , adenosine receptor , chemistry , nociceptor , medicine , endocrinology , stimulation , adenosine a1 receptor , pharmacology , nociception , theophylline , receptor
1 We describe here the effects of intrathecal selective adenosine receptor agonists on acute and more persistent evoked responses of dorsal horn nociceptive neurones recorded in intact rats anaesthetized with halothane. 2 The effects of the A 1 receptor agaonist, N 6 ‐cyclopentyladenosine and the non‐selective agonist 2‐chloroadenosine as well as the A 2a receptor agonist, 2‐ p ‐(2‐carboxyethyl) phenethylamino‐5″‐N‐ethylcarboxamidoadenosine hydrochloride were gauged on the C‐, Aδ‐, Aβ‐fibre, post‐discharge and wind‐up responses produced by peripheral tanscutaneous stimulation. The antagonists, theophylline and 8( p ‐sulphophenyl) theophylline were also tested alone and to reverse the agonist effects. 3 Subcutaneous formalin (5%) was used to produce a more prolonged nociceptive response initiated by peripheral inflammation. 4 Both N 6‐ cyclopentyladenosine and 2‐chloroadenosine produced inhibitions of the C‐fibre evoked responses, wind‐up and post‐discharge of the neurones with no significant effects on the AP responses. By contrast, the Aδ evoked responses were facilitated over the same time course and dose‐range as the inhibitions. N 6 ‐cyclopentyladenosine was more potent and effective than 2‐chloroadenosine. In marked contrast to these agonists, the A 2a agonist produced only weak non‐specific inhibitions. Theophylline and 8( p ‐sulphophenyl) theophylline alone had no effect on the acute responses but prevented or reversed inhibitory effects of N 6 ‐cyclopentyladenosine. 5 The formalin response was markedly inhibited by spinal N 6 ‐cyclopentyladenosine with both the acute first phase and more prolonged second phase being dose‐dependently inhibited. N 6 ‐cyclopentyladenosine was considerably more potent on the formalin response than on the other neuronal measures. 6 The results suggest a role of adenosine A 1 receptors in the modulation of both acute and inflammatory nociception in the spinal cord.