A Neurotoxicologic Evaluation of the Spinal Cord After Chronic Intrathecal Injection of R-Phenylisopropyl Adenosine (R-PIA) in the Rat

Studies in animals have shown that the adenosine receptor agonist R-phenylisopropyl adenosine (R-PIA) induces antinociceptive effects after intrathecal administration. Before such a potentially antinociceptive drug could be considered for intrathecal injection in humans, a neurotoxicologic examination of the spinal cord must be performed in animal models. Rats were injected once every day for 14 consecutive days with R-PIA or saline (controls). The number and density of neuronal cells were calculated by using light microscopy, and further examined with electron microscopy. The "disector method," which is an unbiased stereologic estimator of cell number and mean cell volume, was used for quantitative morphometric analyses. With this technique no significant changes could be seen in rats that had received R-PIA as compared to control rats. We conclude that no significant histologic changes could be detected after chronic intrathecal administration of R-PIA.