The insula, a key brain region in the chronification of migraine

Migraine is a complex brain disorder and highly common. In some individuals with chronic migraine, the headaches occur on up to 15 days or more per month. Despite the various research done on migraine, the specific region of the brain related to it is yet to be discovered. Indeed identifying the regions of the brain that are involved in migraine is important as it will help to develop more targeting therapy and neuromodulation of migraine. It is presumed that the insula, a cortical hub with various functions, is involved in processing the complex symptoms experienced during a migraine. In addition, structural changes have been observed in the insula of individuals with migraine and it varies based on gender. Till date, only a few studies have been done on the insula in individuals with migraine.

In this study, Zhihua Jia collaborated with Shengyuan Yu, Wenjing Tang, and Dengfa Zhao all from the Department of Neurology, The First Medical Center, Chinese PLA (People’ Liberation Army) General Hospital carried out advanced functional magnetic resonance imaging studies  (fMRI) to explore the resting state functional connectivity (FC) of the insula with other regions in the brain using migraine model rats. The research team found an increase in the FC of the insula with different regions of the brain in migraine model rats compared to the control. Their work is published in the Journal of Molecular Pain.

To stimulate meningeal afferents in the experimental group of rats, the researchers used an infusion of inflammatory soup (IS) and prepared animal models with both episodic and chronic migraine. They observed that there was a significant increase in the FC between the insula and cerebellum of rats in the IS group compared to the control. In addition, they also noticed that in the ictal period, there was an increase in the FC between the insula and the medulla and thalamus of low frequency IS rats compared to the low frequency control rats. However, in the high frequency IS group, the increase in the FC was noticed between the insula and several areas of the brain including the midbrain, thalamus, pons, temporal association cortex and the sensory, visual and retrosplenial cortex.

In the model rats with episodic migraine and chronic migraine, the authors compared the alterations in the FC of the insula with other brain regions. They found that in the ictal phase the low frequency IS group demonstrated an increase in the FC of the insula with subcortical regions of the brain that are associated with the trigeminovascular pain pathway. However, in the high frequency IS group the areas of the brain that were involved in migraine were the cognitive processing area (which includes the retrosplenial and temporal association cortex), the central pain pathways (which includes the midbrain, pons, sensory cortex and thalamus) and the pain modulation area.

In summary, the findings of this novel research support the team’s hypothesis that migraine headache phase is dependent on the activation and sensitization of the trigeminovasular pathway. The results suggest that the chronification of migraine is related to limbic cortices and higher brain centers. Therefore, they propose that the involvement of the insula in the headache phase and chronification of migraine may be a potential target for therapeutic agents for migraine.