Behavior induced by putative nociceptive neurotransmitters is inhibited by adenosine or adenosine analogs...

Adenosine agonists administered systemically, intracerebroventricularly and intrathecally have been demonstrated to induce antinociception. Results from studies utilizing intrathecal administration of adenosine or adenosine analogs, in particular, suggest that endogenous adenosine may inhibit the transmission of nociceptive impulses at spinal sites. The present investigations were performed to extend our understanding of the role of adenosine in antinociception by examining the effect of adenosine agonists on behavior induced by two putative spinal nociceptive neurotransmitters, substance P and N-methyl-D-aspartate. Coadministration of each of several adenosine agonists with substance P or N-methyl-D-aspartate intrathecally significantly decreased the intensity of behaviors induced by putative nociceptive neurotransmitters in mice. Adenosine agonist-mediated inhibition was antagonized by theophylline supporting adenosine agonist interactions with cell membrane surface adenosine receptors. Rank order potencies were determined for several adenosine analogs with varying selectivity for A1 and A2 adenosine receptor subtypes. However, rank order potencies did not correlate well with rank order potencies reported previously for adenosine receptor subtypes in biochemical assays. The results of these investigations demonstrate that adenosine inhibits behavior induced by nociceptive neurotransmitters interacting with spinal substance P or N-methyl-D-aspartate receptors. Furthermore, observations provide additional support for endogenous antinociceptive pathways that utilize adenosine at spinal sites.