Anesth Pain Med.  2017 Jul;12(3):224-229. 10.17085/apm.2017.12.3.224.

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

• Yoo SH
• Chung JH
• Seo Y
• Choi MK
• Choi WK
• Kim JB

• KMID: 2388836
• DOI: http://doi.org/10.17085/apm.2017.12.3.224

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.

Keyword

Microscopic; Palonosetron; Rats; Spinal injections

MeSH Terms

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
Receptors, Serotonin, 5-HT3
Serotonin

Figure

• 

  Fig. 1 Light microscopy of rat spinal cords stained with toluidine blue. (A, B) Spinal cord of a administered rat normal saline (A: 100×, B: 400×). (C, D) Spinal cord of a rat administered palonosetron-HCl (C: 100×, D: 400×). A and C demonstrate no identifiable hemorrhage and no necrosis, but C has many vacuoles (arrows) in the dorsal funiculus. B has normal myelin and axons. D has thinly myelinated, swollen, and degenerating axons (arrows).

• 

  Fig. 2 Electron microscopy of rat spinal cords. The spinal cord of a rat administered normal saline (A) and a rat administered palonosetron-HCl (B–D). (A) Compact and myelinated axons. (B) Myelinated axons with separation of the inner lamellae (arrow) creating fluid-filled spaces within the myelin. Axons surrounded by glial cell (arrow head). (C) Thinly myelinated spinal cord with swollen axons (arrow head) and intramyelinic fluid accumulation (arrow). (D) Hypertrophied and degenerated mitochondria (arrow) in the thinly myelinated axon. Black bars represent 1 μm in A and C, 2 μm in B, and 0.5 μm in D.

• 

  Fig. 3 Light and electron microscopy of the intrathecal catheter in both groups. (A) Light microscopy (40×) of the intrathecal catheter (arrow). (B) and (C) Electron microscopy of tissue surrounding the intrathecal catheter. A macrophage (arrow) can be seen in B, and neutrophils in C (arrows). Black bars in B and C represent 2 μm.

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