Morphologic changes in the spinal cord following intrathecal palonosetron-HCl injection in rats.
10.17085/apm.2017.12.3.224
- Author:
Sie Hyeon YOO
1
;
Jin Hun CHUNG
;
Yonghan SEO
;
Min Kyung CHOI
;
Won Kyu CHOI
;
Jong Bun KIM
Author Information
1. Department of Anesthesiology and Pain Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
- Publication Type:Original Article
- Keywords:
Microscopic;
Palonosetron;
Rats;
Spinal injections
- MeSH:
Anesthesia, General;
Animals;
Axons;
Brain Stem;
Catheters;
Humans;
Injections, Spinal;
Male;
Microscopy;
Microscopy, Electron;
Mitochondrial Swelling;
Myelin Sheath;
Nausea;
Postoperative Nausea and Vomiting;
Rats*;
Rats, Sprague-Dawley;
Receptors, Serotonin, 5-HT3;
Serotonin;
Spinal Cord*;
Spine;
Substantia Gelatinosa;
Vacuoles;
Vomiting;
White Matter
- From:Anesthesia and Pain Medicine
2017;12(3):224-229
- CountryRepublic of Korea
- Language:English
-
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 µl of normal saline (N group, n = 6) or 20 µl (1 µg) 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.