Altered effects of an A1 adenosine receptor agonist on the evoked responses of spinal dorsal horn neurones in a rat model of mononeuropath

Abstract

There is clinical evidence that adenosine might be a useful treatment for neuropathic 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 A1 receptor agonist, N6-cyclopentyladenosine (CPA), on the evoked responses of dorsal horn neurones after nerve injury in vivo. Two weeks after surgery, the responses of dorsal horn neurones to controlled electrical and natural (mechanical and thermal) stimuli 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 thermal-evoked responses in both groups, but only minor inhibitions of the Aβ-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 Aδ-fiber-evoked neuronal responses in sham-operated animals, yet this effect was completely absent after nerve injury. These results suggest that nerve injury induces plasticity in the spinal A1 receptor system, which might form the basis for the therapeutic use of adenosine.