UAB Magazine Weekly - Features on Research
Answers from a Headache Expert
By Matt Windsor | Illustrations by Ron Gamble
1. Migraine Doesn’t Fit the Stereotypes
“Migraine is not just one type of headache,” says neurologist John F. Rothrock, M.D., director of the UAB Headache Treatment and Research Program. “It implies a spectrum of headache. A migraine attack may involve visual aura only, without any head pain, or it can involve what everyone thinks of as ‘migraine’—a throbbing, sickening, and very, very severe headache. Or it can be anything along the spectrum between those two extremes—including a relatively mild headache that precisely resembles a tension-type headache. Besides that, in individual patients the migraine follows its own particular path as the months and years pass. At some point some patients find their headache disorder may “transform” from episodic migraine to chronic migraine. Of these, some spontaneously may remit back to episodic migraine. It’s a dynamic disorder that changes its clinical pattern over the person’s lifetime.”
2. Migraine Is the Result of a Hypersensitive Brain
Most physicians—including experts in headache medicine—used to believe that migraine was caused by cranial blood vessels expanding and contracting, Rothrock says. “It was thought that migraine-associated constriction of blood vessels reduced blood flow to the eye or brain, producing aura, and that a compensatory dilation of the blood vessels caused the throbbing, sickening head pain.”
But it turns out that migraine is actually “a genetic condition that, as with epilepsy, produces a hypersensitive brain,” Rothrock says. He notes that researchers at Harvard recently reported evidence indicating that electrical events originating in the brain itself may provoke activation of the receptors for head pain that are located “downstream,” within the meninges that cover the brain.
“It appears that a migraine attack may originate within the visual cortex of the brain,” Rothrock says, “with activity generated at that site serving to promote the trigeminal nerve to release neuropeptides that in turn induce blood vessels located in the meninges to leak pro-inflammatory proteins, which activate and further sensitize head pain receptors, which consequently send a message back to the brain that ‘there’s pain out here.’ This to-and-fro, self-reinforcing process—brain to meninges/meninges to brain—builds and builds until finally it wears itself out, or one administers a therapy that blocks the signaling of head pain.”
3. Know Your Triggers
Because people who experience migraine have hypersensitive brains, they are susceptible to changes in their internal and external environments, including shifts in hormone levels, stress or sudden release from stress, over/undersleeping and weather changes—all of which are known migraine triggers.
Although there are certain triggers commonly reported by patients with migraine, no single trigger will cause migraine in all patients, Rothrock notes. Even for a given individual, a proven trigger doesn’t necessarily cause an attack of migraine every time it’s encountered.
“Events that occur in a person’s life may have an enormous influence on how much or little that person’s genetic predisposition to migraine is expressed clinically,” says Rothrock. “We recently published a paper on the topic of migraine triggers, and from the studies that generated that paper we found that no matter what the race, ethnicity, culture, or country involved, the most common trigger of an acute migraine attack is stress. It seems logical to assume that for chronic migraine the same is true: Stress promotes and reinforces the tendency for episodic migraine to turn chronic.” Rothrock suggests that the converse is likely to be true as well: Stress reduction may make a significant contribution towards improving one’s migraine.
4. Caffeine Has Its Place
Although caffeine is commonly reported as a migraine trigger, and chronic overuse of caffeine may promote migraine “chronification,” caffeine can help in the treatment of acute migraine, Rothrock notes. During an acute migraine attack, drugs may pass more slowly from the stomach to the small intestine, where they are absorbed. Drinking a caffeinated beverage can get the stomach moving again, increasing the likelihood of a positive treatment response, says Rothrock.
5. Education Is Key
While he was working at the University of South Alabama, Rothrock and colleagues there conducted a study to determine whether adding patient education to regular medical management could help migraine sufferers. One hundred clinic patients received either standard treatment or standard treatment plus a three-class course in migraine causes and management. After six months, the patients who took the classes reported fewer and less painful headaches, used less medication, and made fewer unscheduled visits for acute headache treatment than their peers who received standard treatment alone. “At least from these results, it appears that migraine patients benefit greatly from being educated about their disorder,” Rothrock says.
Learn more about migraine causes and treatment here.
Learn more about the UAB Headache Research and Treatment Program.
Treating Chronic Migraine with Botox
By Matt Windsor
You’ve probably already heard about the latest migraine treatment—in a slightly different context. In October 2010, the U.S. Food and Drug Administration (FDA) approved the use of Allergan’s anti-wrinkle drug Botox-A—properly known as onabotulinumtoxin-A—for the prevention of chronic migraine. As opposed to the more familiar episodic form, chronic migraine implies that the afflicted individual has experienced at least 15 days of headache per month for at least three consecutive months. That makes Botox-A the only FDA-approved treatment for a condition that affects as many as 6 million Americans and is the most common reason for referral to a specialized headache clinic, says neurologist John F. Rothrock, M.D., director of the UAB Headache Treatment and Research Program.
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In this video, UAB neurologist John Rothrock explains how Botox injections can treat migraine—and two of his patients discuss their experiences. Watch larger version of video.
In studies conducted while he was on the faculty at the University of South Alabama and now at UAB, Rothrock helped to demonstrate the safety and efficacy of Botox-A as a preventive therapy for chronic migraine. This effort complements his work performed more than two decades ago, when he assisted in the development of self-administered injectable sumatriptan (marketed commercially as Imitrex, Sumavel, or their generic equivalent). Injectable sumatriptan is a safe and highly effective therapy for acute, severe migraine headache, Rothrock says, and its introduction has empowered millions of individuals with migraine to terminate migraine attacks that otherwise would have required a visit to an emergency room (ER) or simply “suffering in silence” at home.
Could Higher Costs Lower Auto Fatalities?
By Nicole Wyatt
The high price of cheap gas: Research by UAB's Michael Morrisey and others found that gas prices and auto fatalities seem to be inversely proportional. That is, as the price of gas rises, fewer people die on the roads.
As gas prices rise, so do the tempers of many drivers. This spring, the average price of a gallon of unleaded gasoline rose nearly a dollar compared to a year ago. And even though prices have fallen slightly in the past few weeks, they are still close to record highs.
The news isn’t all bad, however. While the rising prices may make saving money difficult, they could help save lives by reducing the number of motor-vehicle fatalities. Michael Morrisey, Ph.D., director of UAB’s Lister Hill Center for Health Policy, helped shed light on the silver lining in a study with the UAB Injury Control Research Center. Just a ten-cent sustained increase in gas prices reduced motor-vehicle fatalities per capita by a total of 2.3 percent over two years, he says.
Less Blood on the Highway
“As careful as the enforcement of speeding and drunk-driving laws is, one thing that has changed over the last few years is that gas prices are higher,” Morrisey explains. “In turn, fewer people are on the roads, and drivers are combining trips. As a consequence, there’s less opportunity to have a crash and die.”
The opposite seemed to be true when Morrisey and his fellow researchers began studying gasoline prices. “We had seen evidence that many public-policy interventions were effective in reducing fatalities, but the trend in fatalities per capita wasn’t falling,” he says. “As economists, we looked for reasons that could explain that, and declining real gas prices in the late 1990s and early 2000s were an obvious candidate.”
UAB Imaging Lab Explores Science in HD
By Grant Martin
Melissa Chimento has seen the face of the enemy, and that enemy looks like—a finger. Chimento, a UAB alumna, is an electron microscopist in UAB’s High Resolution Imaging Facility (HRIF), a technology-packed lab in the Shelby Biomedical Research Building that offers researchers the chance to see their work up close and personal, even when the object of their attention is thousands of times smaller than the diameter of a human hair.
A male (right) and female fruit fly are shown at more than 75 times their size by using laser confocal microspy. To view this and other images from the HRIF, scroll down and click the arrows in the slideshow below.
At the controls of an FEI Tecnai T12 TEM, Chimento has captured images of anthrax, adenoviruses, and Mycobacterium tuberculosis, the potentially lethal bug that causes tuberculosis—looking remarkably fingerlike (and quite nonthreatening) in its native environment.
Each year, hundreds of researchers pay a visit to the HRIF, says Kent Keyser, Ph.D., who directs the facility and UAB’s Vision Science Research Center. Vision researchers are regular users of the lab’s equipment, which includes two electron microscopes and several high-powered light microscopes, but its users also include scientists from the Comprehensive Cancer Center, Rheumatic Disease Core Center, Hepatorenal Fibrocystic Disease Core Center, Cystic Fibrosis Center, Biomatrix Engineering and Regenerative Medicine Center, and many others, Keyser notes. These centers also provide monetary support for the facility, Keyser adds, “which is critically important in helping keep fees low while maintaining a high standard of service.”
Seeing Is Believing
Researchers come to capture details of cellular processes and to take advantage of the HRIF’s ability to create two- and three-dimensional reconstructions and animations and record time-lapse video, among dozens of other applications. The devices necessary to do this “are all very expensive, so placing the equipment in a shared core facility ensures that it is accessible to scientists from all different labs across campus, as well as scientists from other universities and institutions,” explains HRIF microscopist Shawn Williams.
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New Facility Aligns Interdisciplinary Researchers in Fight Against Blindness
By Grant Martin
Paul Gamlin, chair of the Department of Vision Sciences, is one of several researchers who will share space in the new EyeSight Foundation of Alabama Vision Science Research Laboratories
When officials from the UAB schools of optometry (UABSO) and medicine dedicated a newly renovated research space in Volker Hall this past fall, it signaled more than just an expansion of laboratories. The state-of-the-art facility marked the start of a historic collaborative arrangement designed to break through the current limitations of vision science research and bring the scientific world closer to a full understanding of the diseases that cause blindness.
The EyeSight Foundation of Alabama Vision Science Research Laboratories will provide space for 15 researchers—including six from the UABSO’s Vision Science Research Center—who formerly occupied separate laboratories in the Callahan Eye Foundation Hospital, Worrell, Shelby, and Spain-Wallace buildings. “Our Vision Science Research Center has long been known for its innovative approaches through interdisciplinary research efforts,” says UABSO interim dean Rodney Nowakowski, O.D., Ph.D. (’75). “This new facility will accelerate many of our ongoing projects by bringing the participating researchers together in the same space. Our hope is that this arrangement will also help generate new ideas and new lines of inquiry for future research endeavors.”
Vision loss stems from a wide variety of diseases, including glaucoma, diabetic retinopathy, and age-related macular degeneration. Scientists in the new vision science research laboratories will focus on examining the underlying pathologies of these conditions and on uncovering the reasons why blinding diseases are so common in the southeastern United States. “The incidence of partial vision loss and blindness is disproportionately high in the Southeast,” says Paul Gamlin, Ph.D., chair of the Department of Vision Sciences, “so UAB is particularly well-suited for this type of facility. We hope to provide the infrastructure for research that will help prevent vision loss throughout the state, region, and nation.”
The facility was created through a $1.2-million grant from The EyeSight Foundation of Alabama, plus additional funds from the provost’s office and the schools of medicine and optometry. The open-lab design concept will enable several faculty members to share large, conjoined lab spaces, creating more opportunities for collaboration.
School of Optometry faculty relocating to the new labs include Paul Gamlin, Ph.D.; Alecia Gross, Ph.D.; Kent Keyser, Ph.D.; Timothy Kraft, Ph.D.; Thomas Norton, Ph.D.; Steve Pittler, Ph.D.; and Om Srivastava, Ph.D. Xincheng Yao, Ph.D., from the School of Engineering, will join them. Faculty from the School of Medicine moving into the new labs include Christine Curcio, Ph.D.; Christopher Girkin, M.D.; Clyde Guidry, Ph.D.; Judith Kapp, Ph.D.; Russell Read, M.D., Ph.D.; Shu-Zhen Wang, Ph.D.; and Yuhua Zhang, Ph.D.
Answering the Call
There are many practical advantages to bringing researchers together into a shared space. Less obvious, however, are the potential advantages that could come from the favorable impression such a facility might have on organizations funding research. After all, collaborative, interdisciplinary efforts between scientists have been commonplace at UAB for years, but having a facility dedicated to those collaborative relationships will increase visibility of the projects, thereby making UAB even more competitive for funding. “While much of the initial focus is on increasing the limits of basic research, there is an increased emphasis from the National Institutes of Health on translational research and even clinical treatments,” Gamlin says. “And the new labs put UAB in position to take advantage of that.”
“When you’re focused on your own area of research, which goes all the way down to the molecular level, it’s easy to wonder, ‘Is what I’m doing ever going to translate into a treatment for disease in my lifetime?’” adds Judith Kapp, Ph.D., the Department of Ophthalmology’s vice chair for basic research. “This facility creates an excellent environment where researchers can work together and imagine how their work is going to translate, and it will keep them focused.”
“The proximity of researchers will foster collaboration,” agrees Steven Pittler, Ph.D., who is currently working on retinal degeneration. “I am trying to understand the basic mechanisms of how the retina functions as well as conducting translational research in finding disease of the retina and related disorders. To have access to other researchers with different areas of expertise, as well as the opportunity to share some specialized equipment will be a huge advantage.”
The research labs were dedicated during a two-day celebration in September, which included a reception, dedication, and lab tour. Additionally, Paul Sieving, M.D., Ph.D., director of the National Eye Institute, was the featured speaker of the Vision Science Symposium, which coincided with the event.