Objective: Sevoflurane, a volatile inhaled anesthetic, is used clinically for general anesthesia in humans. However, the mechanism of action of sevoflurane is not fully understood. We used transcranial flavoprotein fluorescence imaging to visualize somatic sensory cortex responses to noxious stimuli in mice without and with sevoflurane inhalation anesthesia at different concentrations to investigate sevoflurane effects in mice. Methods: A bipolar stimulating electrode was inserted into the left buccal region of the mouse, and changes in flavoprotein fluorescence intensity in the right somatic sensory cortex were recorded before and after electrical stimulation. Measurements were taken while the mouse was awake, at four levels of sevoflurane concentration (0.5%, 1.0%, 1.5%, and 2.0%; 5 min each), and at 10, 20, and 30 min after the end of sevoflurane inhalation. Results: During the awake period, flavoprotein fluorescence intensities in the right sensory cortex decreased after the onset of electrical stimulation, but after 0.9 s, the fluorescence intensity began to increase, reaching a peak value at 2.1 s. This biphasic response significantly decreased at 0.5% sevoflurane and completely disappeared at sevoflurane concentrations above 1.5%, and restored 10 min after cessation of the sevoflurane inhalation. Furthermore, low concentrations of sevoflurane had little effect on the reduction of receptive fields or the conduction of excitation. Conclusion: We conclude that low concentrations of sevoflurane have little effect on the reduction of receptive fields or the conduction of excitation, and that sevoflurane concentrations above 1.5% completely abolish the sensory cortex response elicited by noxious stimulation.

Cortical spreading depression (CSD) is considered to be the physiological substrate of migraine aura. This study aimed to use the autofluorescence of mitochondrial flavoproteins to image cortical activity in migraine model and normal mice. Electrical stimulation of the brain surface resulted in CSD, which was observed as a slow propagation of changes in oxidative flavoprotein fluorescence on the cerebral hemisphere. CSD was easily repeatedly induced on the cerebral hemisphere over a short period of time in chronic migraine model mice, compared with only once per hour in normal mice. However, CSD could be induced again in these mice after the administration of oxygen. During CSD expression, the mice showed little activity and became listless. Furthermore, stimulation of metabotropic glutamate receptor 1 resulted in fluorescence changes in flavoproteins that extended and propagated like CSDs. In conclusion, this mouse model of chronic migraine showed increased susceptibility to experimentally induced CSD. In addition, CSD consumes large amounts of energy in glial cells, suggesting that oxygen supply may be an important factor in reducing the occurrence of CSD.