Intracerebroventricular injection of an agonist-like monoclonal antibody to adenosine A2A receptor has antinociceptive effects in mice

Adenosine is a modulator of nociceptive pathways, both at the spinal and supraspinal levels. Adenosine A1 and A2A receptors (A1R, A2AR) are expressed in the basal ganglia where they are the target of caffeine, the most widely use psychoactive drug which acts as an antagonist to both types of receptors. Given the controversial role of A2AR versus A1R in modulating pain in brain areas, mice received intracerebroventricular injection of Adonis, an agonist-like monoclonal antibody with high specificity for the A2AR and were subjected to behavioral tests investigating nociceptive thresholds. We report that Adonis led to a significant dose-dependent increase in hot-plate and tail-flick latencies in mice and that such increase was prevented by caffeine and ZM 241385, a specific A2AR antagonist. The Adonis antinociceptive effects were also inhibited by naloxone, a non selective antagonist for opioid receptors, suggesting that Adonis acts, at least in part, through the stimulation of the endogenous opioid system. These results confirm the A2AR as a target for pain control and Adonis as a potential drug with therapeutic interest.