Scientists discover'missing link' for why some migraines happen

Scientists have long speculated on why migraines cause auras – short-lived neurological symptoms which occur before or during migraine attacks – as part of a migraine attack. Now, a recent mouse study suggests that an overlooked communication channel between brain and peripheral nerves may hold the answer for migraine sufferers; over 1 billion people annually will experience migraine with aura symptoms. Sensory symptoms include seeing lights or hearing sounds that don’t exist or experiencing tingling or numbness in one or both limbs. Scientists are well aware that auras are tied to “cortical spreading depression”, or waves of abnormal brain activity which rapidly move across the cortex and temporarily deactivate specific neurons. Waves believed to release chemicals into cerebrospinal fluid (CSF), surrounding and cushioning organ, are believed to cause pain-sensitive nerves outside of the brain to sense pain, though exactly how these substances reached nerve endings remains unknown. Now, scientists have discovered a mechanism by which certain molecules may escape the brain’s protective barriers and reach target sites in other organs. Similarity Between Migraines and Blood Sugar Issues in Genetic RiskFactorsIn a study released Thursday (July 4) in Science, researchers explored where CSF leaves the brain by zooming in on an area called trigeminal ganglion cluster of neurons. This network of cells connects nerves of the face and jaw with brain stem, relaying messages sent from facial nerves. Scientists recently made an important discovery: this nerve bundle also provides an outlet for CSF molecules outside the brain to reach outside. They discovered this by genetically engineering mice with neurons producing proteins that light up when exposed to calcium ions, or simply using mice whose neurons produce proteins which glow under fluorescent lighting conditions. Calcium is essential in brain cell communication; when studying trigeminal ganglion neurons, researchers would inject a tracer into each mouse brain so they could monitor its CSF flow. They introduced a substance which allows calcium ions to flow into neurons and activate them, and observed CSF appear about four minutes post injection followed by an exponential surge in calcium-driven activity. This discovery provided direct proof that CSF can transport molecules outside the brain through this channel and make contact with ganglion near its brainstem. Researchers discovered a unique form of ganglion that did not possess its normal outer barrier – something seen elsewhere along its length, according to their mouse studies. Their work suggests that abnormal brain activity causes waves that release pain-inducing molecules out of the brain onto nearby sensory nerve bundles and trigger pain signals in response. (Image credit: Courtesy of Martin Kaag Rasmussen). In order to connect cortical spreading depression to migraine, our team examined its effects. Researchers demonstrated how it could increase CSF flow to an affected area, carrying with it more proteins and molecules to reach the trigeminal ganglion than usual and potentially driving pain and inflammation. “During aura episodes, proteins that activate and sensitize sensory nerves are released into the cerebrospinal fluid and transported to the trigeminal ganglion where they activate pain-mediating sensory nerves,” Martin Kaag Rasmussen of Copenhagen University’s postdoctoral scholar told Live Science via email. “CGRP is what drives migraine, connecting aura phase to headache,” according to Professor Lipton. Although 12 proteins were discovered that activate pain-sensing nerves, only calcitonin gene-related peptide (CGRP) remains as an avenue for potential therapies against migraine. Anti-CGRP medication helps relieve migraine symptoms in about half of patients, yet millions still lack access to an effective remedy. Rasmussen remains hopeful that new molecules found during his study could provide potential solutions. “When patients do not respond well to existing therapies, I believe this may be because we have not identified which molecule(s) are contributing to their headache,” according to him. “This study is extremely exciting because it opens a potential new route for transport of molecules between brain and peripheral ganglia,” stated Andrew Russo, professor of neurology at University of Iowa who wasn’t involved with study but spoke with Live Science about it. Russo noted this finding could extend far beyond migraines; however, all experiments conducted by his group involved mice rather than people; this may explain their successes since mouse brains “are much smoother”. Human brain tissue contains more folds, so abnormal waves associated with migraine cannot travel as quickly. Russo suggested this might affect how quickly CSF exits the brain and whether or not it activates pain-sensitive nerves; next steps include investigating these processes using human and more human-like animal models. Researchers want to take an in-depth look at the new pain-triggering proteins they identified both for migraines and other headache disorders. Are You Curious About Health Desk Q’s or Freckles Coming Out in Sun Light? Submit Your Body-related Queries To Us At [email protected] And See It Solved On Live Science’s Site! We’d be glad to answer them all here on Health Desk Q!