Abstract text (incl. figure legends and references)
Questions: There is a bidirectional link between sleep and migraine with poor sleep reported as both a migraine trigger and symptom. Orofacial allodynia, or hypersensitivity to a non-painful stimulus, is a commonly reported migraine symptom. This study aimed to determine whether sleep deprivation results in orofacial allodynia and whether the arousal promoting neuropeptide orexin-A can recover this.
Methods: Mice were sleep deprived for 6 hours using the gentle handling method or allowed to sleep as usual (n = 12 per group). Periorbital mechanical withdrawal thresholds were tested pre and post deprivation using the von Frey assay. In a series of experiments, mice were administered either 100µg/kg orexin-A/vehicle or 20mg/kg caffeine/vehicle intraperitoneal and thresholds were tested 30 minutes post injection. To measure arousal, locomotor activity after administration of each drug was tested using infrared sensors. To establish if this effect is specific to sleep deprivation, orexin-A was administered after delivery of the clinical migraine trigger nitroglycerin.
Results: Caffeine significantly increased gross movements, and both caffeine and orexin-A significantly increased fine movements compared to vehicle. Sleep deprived mice had significantly lower sensory thresholds than non-sleep deprived mice. Injection of orexin-A, but not caffeine, significantly increased thresholds in sleep deprived mice, despite similar effects on arousal. Nitroglycerin significantly decreased thresholds, however orexin-A did not recover this.
Conclusions: These findings demonstrate that sleep deprivation leads to orofacial allodynia in mice. This can be reversed with administration of orexin-A, but not caffeine, indicating that this is unlikely to be driven by arousal. However, orexin-A was not analgesic when delivered after nitroglycerin-induced allodynia. Further research should explore the role of orexin-A in migraine.