Role of Spinal Adenosine Receptors in Modulating the Hyperesthesia Produced by Spinal Glycine Receptor Antagonism

The intrathecal administration of strychnine in rats yields a prominent touch-evoked allodynia. The effects of an intrathecally administered A1 adenosine agonist: N6-(L-2-phenylisopropyl)-adenosine (LPIA) or an A2 adenosine agonist: 5'-(N-ethyl carboxamido)-adenosine (NECA), on this touch-evoked hyperesthesia were examined. Over the range of 0.3-1.0 nmol these agents produced a dose-dependent inhibition of the strychnine-evoked hyperesthesia. This inhibition was reversed following intraperitoneal injection of caffeine, an adenosine receptor antagonist. No statistical differences between LPIA and NECA were recorded. The powerful effect of adenosine analogues on strychnine hyperesthesia occur at doses that have only a mild analgesic effect on the thermally evoked hot-plate response. This effect is in contrast to opioids, which have been reported to be only minimally effective against strychnine-evoked hyperesthesia. The characteristics of the strychnine hyperesthesia appear to mimic the clinical phenomenon observed in patients suffering from sensory dysesthesia following nerve injury and suggest a possible role for the adenosine receptor in certain pain states.