BACKGROUND: Serotonin type 3 receptors are abundant in the dorsal horn of the spinal cord and in the spinal tract of the trigeminal nerve in the medulla. Moreover, the intrathecal (IT) or epidural administration of ondansetron, a selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, might prevent postoperative nausea, vomiting and intrathecal opioid-induced pruritus more effectively than the drug administered systemically. Before new drugs for spinal administration are accepted for clinical practice, experimental neurotoxicity studies must be undertaken. This study was performed in rats in order to reveal the behavioral and morphological signs of spinal cord damage after chronic IT ondansetron administration.

METHODS: Rats were anesthetized using enflurane in oxygen and an 8 cm polyethylene catheter was advanced caudally through the atlanto-occipital membrane under aseptic surgical conditions. Twelve rats were randomly divided into two groups, an ondansetron (O) group (n = 6) and a normal saline (N) group (n = 6). After postoperative 7 days, we started the IT injection of ondansetron 40 µg (20 µl) or normal saline 20 µl once a day over two weeks. Potential changes of spinal cords were evaluated morphologically by light microscopy (LM) and electron microscopy (EM) in addition to behavioral changes.

RESULTS: No rat in either groups showed any motor or behavioral changes during the administration of ondansetron. By LM and EM, all six rats in the O group showed massive neovascularization over the white and gray matters of spinal cords.

CONCLUSIONS: The results suggest that chronic IT administration of ondansetron causes pathologic changes in the rat spinal cord.