Involvement of A 2 adenosine receptors in spinal mechanisms of antinociception

Abstract

Preliminary investigations suggest that spinal adenosine induces significant behavioral effects and may interact with descending antinociceptive systems stimulated by morphine administered intra cerebroventricularly (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 adnosine or adenosine agonists i.t. Rank order potencies were 5′-N 6-ethylcarboxamidoadenosine (NECA) > N 6-(R-phenylisopropyl)-adenosine (R-PIA) > 2-chloroadenosine (CADO) > N 6-(S-phenylisoprophyl)-adenosine (S-PIA) > adenosine. Rank order potencies were identical for adenosine agonists (i.t.) synergism with morphine (i.c.v.)-induced antinociception. Further, i.t. injections of NECA or nitrobenzylthionoisone (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 A 2 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.