Impact of the circadian clock on cluster headaches funded by $2.4 million NIH grant for UTHealth Houston research

The link between severe headaches and the body’s circadian clock in terms of timing and pain thresholds will be studied thanks to a $2.4 million grant from the National Institute of Neurological Disorders and Stroke (NINDS) to UTHealth Houston researchers.

The research is led by two faculty members from the McGovern School of Medicine at UTHealth Houston: Mark Burish, MD, PhD, associate professor in the Vivian L. Smith Department of Neurosurgery, and Seung-Hee Yoo, PhD, associate professor in the biochemistry department. and molecular biology.

The study builds on previous research by Burish and Yoo, funded by the Will Erwin Headache Research Foundation and published in 2023 in the journal Neurology, which revealed that cluster headaches and migraines are strongly linked to the internal clock that regulates bodily processes known as the circadian system. Burish and Yoo became interested in the topic of circadian clock regulation in headaches because of the clear circadian characteristic of patients with cluster headaches.

Cluster headache, which affects 1 in 1,000 people, is an extremely painful disorder that carries a higher risk of suicide than the general population and can have serious consequences on a patient’s quality of life. In previous research, Burish and Yoo found that there was a circadian pattern of cluster headache attacks in more than 70% of participants, with a peak between 9 a.m. and 3 p.m. and seasonal peaks in spring and fall.

“Migraine and cluster headaches, but cluster headaches in particular, have an unusually circadian pattern of attacks,” Yoo said. “And several cluster headache and migraine treatments, like steroids and melatonin, strongly influence the core molecular machinery of our body’s internal clock. We thought these connections were interesting. With Dr. Burish on headaches and my background in circadian biology, we began to discuss new ways to study the circadian characteristics of headaches.

In a preclinical study by the team recently published in Headache, Yoo and Burish discovered a novel circadian pattern of pain in a laboratory mouse model of headache involving nitroglycerin, a drug that can trigger cluster headaches and migraines in these patients. When the clock genes were genetically modified in this laboratory model, the circadian pattern of pain disappeared. Burish and Yoo believe this research, which has been years in the making with funding from the Will Erwin Headache Research Foundation, holds promise as a new model for studying the unusually circadian nature of these headaches.

“The circadian aspect of cluster headaches and migraine is fascinating: Something seems to activate at the same time every day,” Burish said. “One of the goals of our research is to understand this activation, in hopes of one day preventing the occurrence of these headaches. We are grateful to the Will Erwin Headache Research Foundation for providing us with the kind of support long-term research needed to explore a new area of ​​research, and we are very pleased to have now received funding from the NIH.

Burish is also director of the Will Erwin Headache Research Center at UTHealth Houston Neurosciences. Yoo and Burish are faculty members at the University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences.

The grant number for NINDS, part of the National Institutes of Health, is R01NS136677-01.