Adenosine contributes to mu-opioid synaptic inhibition in rat substantia gelatinosa in vitro

The purpose of this study was to investigate the cellular basis of the synergistic anti-nociceptive interaction between adenosine and opioids reported for spinal cord in vivo. Patch clamp recordings from rat substantia gelatinosa neurons in vitro were used to assess whether adenosine receptor antagonists impact upon mu-opioid receptor (MOR)-mediated inhibition of glutamatergic synaptic transmission. The MOR agonist DAMGO inhibited evoked EPSCs and this inhibition was partly reversed by DPCPX, an A1 receptor (A1R) antagonist. The A2a receptor antagonist, ZM241385 had mixed effects on DAMGO-mediated inhibition, producing either a further inhibition or a reversal of the inhibition. These data show that activation of A1R as a secondary consequence of MOR-activation and putative adenosine release will potentiate opioid synaptic inhibition of nociceptive circuitry.