“From a basic clinical point of view, the hub idea really speaks to the notion that there are many inputs and outputs that may be bidirectional with other brain regions,” Borsook said.

Targeted Therapy for the Insula?

“Cortical spreading depression leads to electrical and chemical changes, which are the hallmark[s] of migraine. These include dilation of blood vessels and neurogenic inflammation,” Estemalik said. If the insula is a hub of migraine hyperexcitability, could targeting therapies like deep brain stimulation or transcranial magnetic stimulation (TMS) help?

One 2012 study, published in the journal Clinical Neurophysiology, describes targeting the posterior-superior insula with TMS. The study concluded that this area should be considered as a possible target for chronic pain treatment in future studies.3

“This is a difficult question because the areas of thickening involve multiple areas that have different functions in the insula. If TMS can be targeted effectively, it may prove to be a useful process. Treating this area may be a good option that should be done with appropriate trials,” Borsook said.

More Questions for Future Research

In a previous study, Borsook and his colleagues found that female migraineurs had a thicker insular cortex than male migraineurs, but more work needs to be done to find out if thicker insular cortex is specific to females.2 “We know that migraine is more common in women, but we treat it as if the pathophysiology is the same,” said Estemalik.

Another question is whether other types of chronic pain syndromes have the same or similar effects on the aging of the insular cortex as migraine. Is the insular cortex a hub of multidimensional integration for all chronic pain states? 2

Finally, physicians need to know more about the effects migraine medications may have on cortical thickening. The women in this study were predominantly taking nonsteroidals and triptans to treat their migraines. Would better treatments reduce cortical thickening with age?1

“It is unclear whether the thickening is an adaptive or maladaptive process. One way to further understand this is to observe changes in such patients with effective treatments,” said Borsook.

References

1. Maleki N, et al. Pain. 2015; doi: 10.1097/j.pain.0000000000000159.

2. Seifert F, et al. Pain. 2015; doi: 10.1097/j.pain.0000000000000207.

3. Ciampi de Andrade D, et al. Neurophysiol Clin. 2015; doi: http://10.1016/j.neucli.2012.08.003.