Spinal cord morphology after chronic intrathecal administration of adenosine in the rat

Background: The endogenous compound adenosine is known to have various modu latory effects both in the peripheral and central nervous system. Adenosine and its analogues induce antinociception in animal models when administrat ed systemically and intrathecally (IT), both in acute and chronic models of pain. Before a new drug is introduced for spinal pain treatment in humans, experimental studies of neurotoxicity must be undertaken. Methods: This study was performed in rats in order to reveal morphological or morphometric signs of spinal cord damage after chronic (two weeks) admin istration of adenosine. After insertion of IT catheters, the animals were i njected twice a day during two weeks with adenosine (100 mu g) or saline (c ontrols). Potential spinal neurotoxicity was evaluated morphologically by l ight and electron microscopy supplemented by a morphometric analysis. Results: There were no signs of histologic changes indicating neurotoxic ef fects by any of the methods of analysis. The morphological findings in the adenosine treated rats did not differ in any case from those of the saline treated animals. Conclusion: The results suggest that chronic IT administra tion of a high dose of adenosine is not associated with neurotoxicity in th e rat spinal cord.