Abstract
Postoperative negative affects such as anxiety need to be better understood and treated to improve patient recovery. The present study evaluates the effect of a single exposure to a high-dose of opioid (4×100μg/kg fentanyl injections in 15min intervals resulting in a total dose of 400μg/kg), as used for surgery in humans, on anxiety-like behavior (ALB) in rats. First, the level of anxiety was evaluated 24-h after a high-dose of fentanyl using an elevated plus-maze apparatus. Second, the preventive effect of BN2572, a N-methyl-d-aspartate receptor (NMDA-R) antagonist, and 50% nitrous oxide (N2O), a gas with NMDA-R antagonist properties, was assessed. A significant increase in ALB was observed in fentanyl‐treated rats. Interestingly, fentanyl-induced ALB was prevented by BN2572, suggesting a NMDA-dependant pathway. Fentanyl-induced ALB was also prevented by a single 50% N2O exposure. The present study provides evidence that deleterious outcomes of opioid use, referred to as “post-opioid syndrome”, include not only pain hypersensitivity as previously described, but also negative affects such as anxiety. Since N2O prevents elements of this post-opioid syndrome, we speculate that N2O could be a good therapeutic agent to facilitate postoperative rehabilitation.
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