The Neurological Safety of Intrathecal Acyclovir in Rats

Abstract

Background: Effective early antiviral treatments reduce both acute zoster pain and the risk of postherpetic neuralgia. The authors hypothesized that the direct neuraxial administration of acyclovir could provide superior drug application to the spinal neural structures with a higher viral burden and have various advantages over the other routes of drug administration in terms of required doses, side effects, and efficacy. Objective To know whether intrathecal acyclovir injection is neurologically and histopathologically safe or not. Study Design: Randomized, experimental trial in rats. Setting: Associated experiment center. Methods: A total of 40 rats weighing between 250-300g were used. The rats were randomly divided into 2 groups of 20 each using a random number table: normal saline group (Group N) and acyclovir group (Group A). Rats in Group N were administered 20 mu l of normal saline and Group A were administered the same volume of 700 mu g/mL acyclovir into the intrathecal space via an intrathecal catheter. Saline or acyclovir was administered daily for 5 consecutive days. The changes in behavior and sensory-motor function were checked and histopathological findings of the spinal cords were observed by light and electron microscopy. Results: No rats in Group N or Group A showed any behavioral change or sensory-motor dysfunction during the 5-day observation period. Furthermore, no histopathological abnormalities of the spinal cord were observed in the 6th day after the last intrathecal administration of the drug. Limitations: There is a need to perform studies to evaluate long-term safety by observing cumulative neurotoxic effects with continual injection during a long-term period. Conclusions: There was no evidence of neurological and histopathological abnormalities following intrathecal acyclovir injection.