Despite being one of the most common neurologic disorders in the world, much remains unknown about migraines. It’s unclear why migraines disproportionally affect women compared to men. Or why the painful symptoms of a migraine attack can manifest in the head, neck and shoulders. Patients report experiencing sensitivity to light and sound, nausea, intense pain in the head and loss of vision when a migraine occurs, but it’s not known if all of these symptoms share one cause or arise from multiple contributing factors.  

There is a common misconception that migraines are just headaches. Those who experience migraines know the difference. Headaches typically inflict mild to moderate pain and last for a few hours to days, but can typically be relieved with over-the-counter medication. Migraines often cause severe, throbbing pain and may need specific medication to treat the intense symptoms.  

Brigham researchers are using innovative research approaches to improve our understanding of the association between migraines and sex hormones, sleep and pain to better inform the development of therapeutics and treatments patients.   

Let’s Talk About Sex Hormones and Migraines 

Carolyn Bernstein, MD, of the Department of Neurology, began exploring the underlying mysteries of migraines well before she joined the Brigham. In the early stages of her career, she worked on translational research uncovering how sensitivity to light, or photophobia, affected patients with migraines and if certain colors of light could improve migraine symptoms.  

Carolyn Bernstein

Bernstein is currently focused on understanding how hormones affect migraines. Males and females produce different sex hormones and it’s theorized that female hormones and menstrual cycles may be a reason why females experience more migraines than males. Bernstein is currently investigating if a pharmacotherapeutic medicine could potentially help to prevent migraines during menstrual periods. Bernstein’s contributions may inform how physicians care for their patients with migraines.  

“We’re tracking estrogen, progesterone and other measures so we can understand how these hormonal changes may influence migraine severity,” says Bernstein. “We’re actively recruiting participants for the study and by the end of it, we hope to have a better idea of how hormones affect different people who are receiving the drug versus those who are not.”  

Don’t Hit Snooze on Migraines 

Suzanne Bertisch, MD, MPH, of the Division of Sleep and Circadian Disorders, and Angeliki Vgontzas, MD, of the Department of Neurology, began working together in 2018 after finding a shared interest in headaches and migraines. Combining their clinical and research expertise, they rely on each other to guide their research initiatives, which include investigating the effect napping and sleep have on patients with migraines.  

Angeliki Vgontzas

Suzanne Bertisch

“Our partnership works so well because we have a shared goal of improving the quality of life for patients with migraines and headaches,” says Vgontzas. “Migraines are underdiagnosed and underrecognized and our work is helping physicians and patients understand the invisible illness.”  

Since they began working together, the researchers have examined whether sleep impacts migraine occurrence among patients with episodic migraine. Study participants wore a device that collected continuous, nightly sleep metrics and tracked their sleep and headaches for six weeks. Using the data, the study team then evaluated how nightly sleep relates to the occurrence of same-day and next-day migraine attacks among those with episodic migraines.  

“Through this work, we weren’t able to find a strong association between sleep and migraines,” says Bertisch. “We know, in general, people who have poor sleep tend to experience headaches. However, we didn’t uncover night-to-night evidence through our study. The migraine-sleep intersection is still unclear, but we’re passionate about uncovering more in this area.” 

The pair is currently working on the Hispanic Community Health Study/Study of Latinos, a long-term epidemiologic study of 15,000 U.S. adults who identify as Hispanic or Latino, analyzing migraines in the Hispanic and Latino populations. In addition, Vgontzas is currently examining the healthcare disparities of migraine care. 

A Pain in the Neck 

William Renthal, MD, PhD, of the Graham Headache Center at Brigham and Women’s Faulkner Hospital and Department of Neurology at Brigham and Women’s Hospital, is working to uncover the genes and cell types associated with migraine pain. He is also the director of the Harvard PRECISION Pain Center, a multi-institutional network of clinicians and scientists studying molecular features that contribute to chronic pain and headache, where he and his group can examine human samples using cutting edge molecular technologies to identify new targets for migraine therapeutics. 

Will Renthal

Kevin Hodgetts

Toward this goal, Renthal is collaborating with Kevin Hodgetts, PhD, a medicinal chemist in the Department of Neurology, to develop precision therapeutics for patients with chronic headache and pain disorders.  

“Our collaboration story really starts with being in the same place at the right time,” says Renthal. “Mass General Brigham has an infrastructure that puts talented people together in the same room and creates opportunities for this type of synergy. The relationship with Kevin continued to grow through our shared interests and through our willingness to accept opportunities as they arise.”  

In his medicinal chemistry lab, Hodgetts works with physicians and researchers to discover new drugs for neurological diseases. Leveraging the biological targets for migraine that Renthal discovered, the pair is using their combined strengths and resources to identify and modify potential therapeutics that can interact with those targets at the cellular level in human models.  Some of the biological targets Renthal discovered are inside and outside of the brain, so they are identifying molecules that can pass through the blood-brain barrier or, in some cases, keep the potential drug out of the brain. 

Currently, the team is working on preclinical studies to advance their lead compounds and to uncover additional genetic and cellular targets that could help guide new, more personalized treatments for patients with migraine and chronic pain. 

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