THE ROLES OF SPINAL ADENOSINE RECEPTORS IN THE CONTROL OF ACUTE AND MORE PERSISTENT NOCICEPTIVE RESPONSES OF DORSAL HORN NEURONS IN THE ANESTHETIZED RAT

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(2 alpha) receptor agonist, 2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride were gauged on the C-, A delta-, A beta-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 A beta responses. By contrast, the A delta 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(2 alpha) 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.