Morphologic changes in the spinal cord following intrathecal palonosetron-HCl injection in rats

Abstract

Background: Intravenous palonosetron-HCl, a second-generation antagonist of selective serotonin type 3 (5-HT3) receptors, can prevent chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). 5-HT3 receptors are abundant in the lower brainstem and the substantia gelatinosa of the spinal cord, which provides a theoretical rationale for neuraxial administration of 5-HT3 receptor antagonists for CINV, PONV, and opioid-induced nausea and vomiting. However, there are no reports of neuraxial administration of palonosetron-HCl. Before neuraxial administration of a drug is accepted for clinical use, its safety must be proven. This study was conducted to determine whether neuraxial administration of palonosetron-HCl produces neurologic injury. Methods: Male Sprague-Dawley rats under general anesthesia were catheterized intrathecally and the catheter tip was advanced caudally to the L1 vertebra. After 7 days, 20 l of normal saline (N group, n = 6) or 20 l (1 g) of palonosetron-HCl (P group, n = 6) were injected intrathecally once per day for 2 weeks. Neurotoxic changes were evaluated by light microscopy (LM) and electron microscopy (EM) of the spinal cord. Behavioral changes were also evaluated in both groups. Results: One of the N group rats and three of the P group rats demonstrated abnormal behavior during intrathecal drug injection, but otherwise their behavior was normal. The spinal cords of the N group did not have any abnormal findings by LM or EM. The spinal cords of the P group had multiple vacuoles in the white matter by LM, especially in the dorsal funiculus, and EM revealed myelin, axonal, and mitochondrial swelling. Conclusions: Results suggest that chronic intrathecal administration of palonosetron-HCl produced microscopic morphologic changes in the spinal cords of rats.