Sex-specific electrophysiological and behavioral responses to nitrous oxide in a murine model of neuropathic pain.
Biology of Sex Differences July 7, 2026 Gemma González-Hernández, S. Torres-Sánchez, D. Sanchez-Morillo et al.
Nitrous oxide (N₂O) at 50% concentration for one hour produced sex-specific effects on behavior and brain activity in mice with chronic pain. In males with neuropathic pain, N₂O reduced pain sensitivity, while females showed no pain relief. The drug decreased movement in both sexes, with longer-lasting effects in males. Brain recordings showed N₂O reduced low-frequency electrical activity in all mice, with stronger effects in females. In animals without pain, N₂O dampened brain responses to stimulation, but in pain-model mice it restored prefrontal activity. No antidepressant-like effects appeared 24 hours after treatment in either sex. These results indicate that N₂O's effects depend on sex and pain state, emphasizing the need to consider sex in NMDA receptor-based treatments.