Classification of adenosine receptors mediating antinociception in the rat spinal cord

Abstract

1 Analogues of adenosine were injected intrathecally into rats implanted with chronic indwelling cannulae in order to determine a rank order of potency and hence characterize adenosine receptors involved in spinal antinociception. 2 In the tail flick test l-N⁶-phenylisopropyl adenosine (l-PIA), cyclohexyladenosine (CHA) and 5′-N-ethylcarboxamide adenosine (NECA) produced dose-related antinociception which attained a plateau level. NECA and CHA also produced an additional distinct second phase of antinociception. d-N⁶-Phenylisopropyl adenosine (d-PIA) and 2-chloroadenosine (CADO) had very little antinociceptive activity in this test. The rank order of potency in producing the plateau effect was l-PIA > CHA > NECA > d-PIA = CADO, while that for the second phase of antinociception was NECA >-CHA. 3 Pretreatment with both theophylline and 8-phenyltheophylline (8-PT) antagonized antinociception produced by CHA, with 8-PT being at least an order of magnitude more potent than theophylline. Both antagonists produced a significant hyperalgesia in the tail flick test. l-PIA and CHA also produced methylxanthine-sensitive antinociception in the hot plate test. 4 These results suggest that activation of A₁-receptors in the spinal cord can produce antinociception. Activation of A₂-receptors may produce an additional effect, but the relative activity of CHA in this component of activity is unusual.