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- W2184902017 abstract "Background: Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematicevaluationofspinalanalgesicsafetyindevelopmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long-term function after intrathecal morphine in the neonatal rat. Methods: Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P) 3, 10, and 21. The relationshipbetweeninjectatevolumeandsegmentalspreadwas assessed postmortem and by in vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measuredatbaselineand30minafterintrathecalmorphine.To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis, and glial response were evaluated 1 and 7 days after P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Results:Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally mediated analgesia at all ages with lower dose requirements in younger pups. High-dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. Conclusions: The therapeutic ratio for intrathecal morphine (toxic dose/antinociceptive dose) was at least 300 at P3 and at least 20 at P21 (latter doses limited by side effects). These data provide relativeefficacyandsafetyforcomparisonwithotheranalgesicpreparations and contribute supporting evidence for the validity of this preclinical neonatal safety model." @default.
- W2184902017 created "2016-06-24" @default.
- W2184902017 creator A5041275640 @default.
- W2184902017 creator A5041587364 @default.
- W2184902017 creator A5042389999 @default.
- W2184902017 creator A5052669575 @default.
- W2184902017 creator A5090074550 @default.
- W2184902017 date "2010-01-01" @default.
- W2184902017 modified "2023-10-12" @default.
- W2184902017 title "Effects of Intrathecal Morphine in the Neonatal Rat" @default.
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