Why are migraines worse during your period? Research in mice points to a hormone called progesterone and offers a brand new treatment goal

Migraines are throbbing headaches often accompanied by nausea and increased sensitivity to light, noise and touch. Nearly 30 million Americans suffer from migraines and almost one in 4 have a minimum of 4 severe seizures per 30 days. Three times as many ladies suffer from migraines like men, and this difference is much more pronounced throughout the reproductive years.

migraine often occur across the menstrual cycleduring which the degrees of reproductive hormones corresponding to progesterone and estrogen rise and fall. The levels of those two hormones are low throughout the perimenstrual phase.

Some patients suffer from headaches exclusively during menstruation, Menstrual migraine. These migraine attacks are often more severe and difficult to treat than attacks before or after menstruation. Recurrent migraine attacks increase the chance of chronic migraineUncontrolled migraines can even increase the chance of Headaches attributable to excessive medication use.

We are researchers who study how Progesterone regulates neuronal function in health and disease. Our research in recent times has focused on understanding how this hormone and its receptors affect the brain. In our recently published research on mice, we found that progesterone in individuals who menstruate more prone to migraines.

Progesterone and pain sensitivity

First, we investigated whether pain sensitivity in female mice changes during their reproductive cycle. Female mice experience cyclical hormonal changes throughout the so-called Estrous cycles which last 4 to 5 days.

To do that, we attached thin wires of accelerating weight to the hind paws of the mice to find out their sensitivity to the touch. The mice signaled discomfort by pulling their paw back. We found that Pain sensitivity was higher in mice at the tip of the cycle, when reproductive hormone levels are low, in comparison with mice in the midst of the cycle, when reproductive hormone levels are high.

Next, we tested whether progesterone increased pain sensitivity. We removed the mice's ovaries to rule out internally driven hormonal changes. Since an estrogen surge precedes progesterone release throughout the female reproductive cycle, we administered estrogen followed by progesterone or saline. We found that animals treated with progesterone increased sensitivity to the touchbut not the animals treated with saline solution.

Progesterone takes effect partly by stimulating proteins called progesterone receptors, that are positioned within the brain and slowly modulate the expression of varied genes. Progesterone can even quickly change the way in which neurons work when it breaks down right into a molecule. called allopregnanoloneOur studies suggest that progesterone receptors may play a job within the slow-onset pain-promoting effects of progesterone.

After finding progesterone receptors in neurons which can be a part of the migraine pain pathways within the brain, we next desired to know whether these receptors regulate migraine susceptibility. In mice without progesterone receptors In their brains, progesterone didn’t reduce their pain threshold. In contrast, activating progesterone receptors with a drug that specifically targets these receptors increased pain sensitivity. Progesterone regulated sensitivity to mechanical and cold stimuli, but not sensitivity to heat and light-weight stimuli.

Finally we now have used nitroglycerin to simulate migraine. Nitroglycerin causes symptoms much like those experienced by migraine victims, and lots of the drugs used to treat migraines also relieve these symptoms in animals. When we stimulated the mice's progesterone receptors, susceptibility to migraines increased. In contrast, mice without these receptors were immune to pain attributable to nitroglycerin.

Possible goals of migraine treatment

Our study identifies progesterone receptors within the brain as one reason why women are susceptible to migraines. Cyclical changes in progesterone levels throughout the menstrual cycle activate the receptor, which may trigger migraines.

This also implies that the progesterone receptor is a possible goal for drugs to forestall or treat migraines. As our team continues to review how progesterone receptors increase pain sensitivity, we hope to search out recent treatment options for migraines.