Altered effects of an A(1) adenosine receptor agonist on the evoked responses of spinal dorsal horn neurones in a rat model of mononeuropathy

There is clinical evidence that adenosine might be a useful treatment for n europathic pain states, although little is known regarding its mechanisms. In this study, we use the selective (L5/L6) spinal nerve ligation model to investigate the effects of an adenosine A(1) receptor agonist, N-6-cyclopen tyladenosine (CPA), on the evoked responses of dorsal horn neurones after n erve injury in vivo. Two weeks after surgery, the responses of dorsal horn neurones to controlled electrical and natural (mechanical and thermal) stim uli were recorded and the effects of intrathecal CPA were compared between nerve-ligated and sham-operated rats. CPA produced significant inhibitions of the C-fiber-evoked response, postdischarge, wind-up, mechanical, and the rmal-evoked responses in both groups, but only minor inhibitions of the A b eta-fiber response. Overall, the drug effects in spinal nerve-ligated rats were greater than those of sham-operated rats. Spinal theophylline reversed these inhibitions. In contrast, CPA produced marked facilitations of the A delta-fiber-evoked neuronal responses in sham-operated animals, yet this e ffect was completely absent after nerve injury. These results suggest that nerve injury induces plasticity in the spinal A(1) receptor system, which m ight form the basis for the therapeutic use of adenosine.