Changes in Cortical Oscillatory Activity induced by Nitroglycerine in Rodent Model of Migraine

Background The nitroglycerin (NTG) rodent model of migraine has been widely used in screening the effectiveness of migraine therapeutics. Electrophysiological recordings from trigeminocervical complex in these models have also been used to understand the mechanisms of pain transduction during migraine and to assess efficacy of treatments. However, such recordings require the animals to be anesthetized throughout the experiment which can be confounding. In this study, we investigate the effect of migraine induced by NTG on cortical oscillations in electroencephalogram (EEG) in awake, behaving animals. Methods Two separate cohorts of rats underwent craniotomies where intracranial EEG screws were implanted to perform recordings from the right and left somatosensory cortices. Cohort 1 (n = 10) was injected with 13 mg/kg NTG, and a control cohort (n = 10) was injected with saline. In all animals, baseline EEG recordings for 30-min was followed by injection of NTG or saline and continuous EEG recordings up to 4 hrs after injection. EEG recordings were interrupted only at 30 min, 2 hrs, and 4 hrs for a 10-min session of spontaneous behavior assessments using the open field test. Results NTG induced significant suppression of power in the low frequencies (< 30 Hz) of cortical EEG compared to saline controls immediately after injection that lasted for 90 min after injection. On the other hand, power in low gamma band of the EEG showed a delayed, but long-lasting significant suppression compared to saline controls starting at 90 minutes and lasting at least 4 hrs after injection. In the high gamma band, however, suppression was initiated within 5 mins from NTG injection and similarly for at least 4 hrs after injection. A significant suppression in locomotor/exploratory behaviors and significant enhancement in anxiety behaviors was also observed in cohort 1 compared to control cohorts with saline infusion. Conclusion This study demonstrated that a 13 mg/kg dose of NTG induced a transient suppression of energy in the low (< 30 Hz) frequencies and sustained suppression of power in the gamma band in the EEG from the somatosensory cortex, which also correlated with sustained behavioral dysfunction observed in a popular rodent model of migraine.