Involvement of A2 adenosine receptors in spinal mechanisms of antinociception

Preliminary investigations suggest that spinal adenosine induces significant behavioral effects and may interact with descending antinociceptive systems stimulated by morphine administered intracerebroventricularly (i.c.v.). In the present study, rank order potencies for antinociception induced by adenosine agonists administered intrathecally (i.t.) were determined. Interactions of adenosine agonists (i.t.) with morphine (i.c.v.)-induced antinociception were also examined. Dose-dependent antinociception, as measured in tail flick and hot plate assays, was observed in mice administered adenosine or adenosine agonists i.t. Rank order potencies were 5'-N6-ethylcarboxamidoadenosine (NECA) greater than N6-(R-phenylisopropyl)-adenosine (R-PIA) greater than 2-chloroadenosine (CADO) greater than N6-(S-phenylisopropyl)-adenosine (S-PIA) greater than adenosine. Rank order potencies were identical for adenosine agonist (i.t.) synergism with morphine (i.c.v.)-induced antinociception. Further, i.t. injections of NECA or nitrobenzylthioinosine (NBI), an adenosine reuptake inhibitor, were able to potentiate morphine (i.c.v.)-induced antinociception. Hind limb paralysis induced by high doses of adenosine agonists (i.t.) was dissociated from antinociceptive effects. Rank order potencies determined in our studies support involvement of A2 adenosine receptors in spinal mechanisms of antinociception. In addition, these results confirm spinal adenosine interactions with antinociceptive systems stimulated by i.c.v. injections of morphine.