Solving the Mystery of Migraines

Carlene Moore’s infectious, loud laughter has been used by the Duke University School of Medicine to study painful conditions, from sunburns and migraines to a severe and painful facial condition called “trigeminal neuralgia.” help offset the serious nature of the ongoing research in our laboratory. suicidal disease. ”

Moore, Assistant Professor of Neurology and member of Duke Brain Science Institutehas spent the past 15 years researching pain.

Moore initially focused on how skin pain, such as sunburn, travels from the epidermis to the brain. But Moore herself suffered from debilitating bouts of what is clinically known as headaches (sephalgia), and her lab is looking to find ways to relieve pain from symptoms that are “more than just headaches.” changed its policy to

More than 1 billion people suffer worldwide Migraine, is the most common neurological disorder and the third most common. However, little is known about what causes migraines.

Part of the problem is that it’s hard to track down. “Migraines are not one thing,” says Moore. “In addition to headaches, it is accompanied by symptoms such as nausea, vomiting and sensitivity to sound and light.”

Since migraine develops over several stages, it is difficult to grasp the stage of onset, and the manifestation of symptoms varies from person to person. “Unlike foot pain, migraines don’t know where they originate.”

Another complicating factor is that migraines primarily affect women. Although three of her four migraine sufferers are female, historically most migraine research has been conducted by male scientists using male research animals, rodents. rice field.

“Until recently, we’ve studied almost exclusively male mice,” Moore said. As of 2016, researchers receiving federal funding from the National Institutes of Health must include both sexes in their studies (or have strong justification to exclude one gender). This policy had a large effect in a relatively short period of time.

“It opened up a field,” Moore said. “We have already discovered different pain mechanisms according to gender.”

Historical limitations aside, researchers like Moore have elucidated several factors that contribute to migraine development. The first important element is the trigeminal nerve, the “all sensor” of the face. These nerves collect all the sensory information from your forehead to your chin and everything in between and send it to your brain for processing. However, you will need an interpreter to say that the coffee you drank is too hot or that your cheek hurts.

Its translators are a family of transient receptor potential (TRP) channels that relay information about the external world, such as taste, temperature, and touch, and encode it in an electrical language that the brain can understand. TRP channels are scattered in trigeminal neurons and are a critical step in the process of migraine pain propagation.

“We are interested in understanding the mechanisms and functions of TRP channels,” said Moore. “It’s about migraine in particular, and how we can develop new treatments for migraine.”

Smooth out wrinkles and relieve pain

One of the surprising ways Moore et al. discovered how to silence TRP channels is with Botox, a muscle-paralyzing toxin commonly used as an anti-wrinkle therapy.

Botulinum toxin, a neurotoxin known as Botox, is often injected into the forehead. Anecdotal reports from the early 2000s reported that people who received Botox for cosmetic purposes were relieved to have no wrinkles or migraines after the treatment. This prompted further research, and in 2010, Moore explained, Botox was approved by the Food and Drug Administration for use as a treatment for chronic migraines.

Botox for migraines provides great relief, much like acupuncture. “This is a series of 31 injections in one session every three months,” Moore said. “You can definitely feel it!”

she would know Ms. Moore was given Botox to relieve her own migraines and prescribed Botox in trigeminal nerve cell dishes taken from mice in her lab. Botox has been an approved migraine treatment for over a decade, but how and why it works is still not fully understood.

Recent work in Moore’s lab In partnership with pharmaceutical company AbbVie, we’ve released some of the first cellular snapshots showing how Botox relieves migraine headaches.

“By soaking the cells in an inflammatory broth, we see that the botulinum toxin has a preferential effect on pain-sensitive cells,” said Moore.

Once inside nerve cells, botulinum toxin appears to weaken pain signals by cleaving a tethered molecule called synaptosome-associated protein 25 (SNP25). This protein helps release packets of neurochemicals and receptors such as TRPV1 and TRPA1 in brain cells.

By interrupting the docking process, Moore believes Botox prevents TRP channels from implanting in trigeminal nerve cells, resulting in fewer interpreters of pain signals to the brain.

family ties

Moore’s migraine research is still in its early stages, but outside the lab, she and her family have long had painful symptoms.

Moore grew up on the Caribbean island of Saint Christopher, the second oldest of five girls. Her father was a welder in a sugar cane factory on the island and her mother was a school cook. Her parents recognized her curiosity in Moore from an early age.

“I’ve always been a very curious person,” Moore said. “I still hear my mother say how curious I was. I question everything about nature. What is it?” was always a question. ”

Moore’s inquisitive personality began her current curiosity about pain in elementary school when her mother was diagnosed with a debilitating herniated disc.

“She was the one who got me interested in the neuroscience of pain,” Moore said. “When I was 9 or 10, she developed a herniated disc and suffered from terrible back pain. I have seen her mother suffer from pain all her life. ”

be engrossed in research

Because St Kitts is a small island with limited medical facilities, Moore’s mother had to travel to England for spinal repair surgery, leaving her five daughters for six months to recover. . That was the beginning of Moore’s second encounter with family pain.

Moore is the second oldest of five daughters, but her older sister was often paralyzed by migraines, so she was given the role of older sister while her mother was away. In fact, all but Moore’s youngest sister experience migraines.

Moore continued her schooling in St. Kitts with a dream of working in medicine, but she kept her focus on science with pain in mind. “At the time, science was all about being a nurse or a doctor,” Moore said.

In 2001, Moore had another life-changing experience while working on his BA in Biology at Midwestern State University in Texas. Summer research internship at the University of Texas at Austin.

“This was my first lab experience and I fell in love with research,” recalls Moore. “Being able to ask questions and actually answer some of them within the day felt like my eyes were opened to the world of research,” she said. “Up until that point, I thought that if you were interested in science and biology, maybe going to medical school was the main route.”

Her internship led her to both a new career path and a commitment to passing on opportunities to the next generation of scientists.

“Internships are really important. That’s one of the reasons I coach summer high school students. Duke University Neuroscience EExperience it,” Moore said. “Knowing how important and impactful my summer internship was, I want to give underrepresented people and other young people the experience I had.”

This internship inspired Moore to switch from medical school to neuroscience, earning a doctorate in neurobiology from the University of Alabama at Birmingham in 2008.

Moore then came to Durham to work as a postdoctoral fellow in the lab of the Duke Neurology Professor and Physician. Wolfgang Riedtke medical doctor. “We wanted to hire someone who was ambitious and who shared our passion to do something challenging for the chance to make a bigger discovery,” Liedke said. “And then I met Carlene and made a deal.”

Under Rietke’s guidance, Moore spent productive scientific time as a postdoc. Among them are Better ointments to treat sunburn pain with TRP antagonists.

“If someone is really good at something, it will look easy,” Rietke said of Moore’s skills as a scientist and ability to collaborate and guide others. “It’s like watching Roger Federer play tennis.”

Moore says that part of his lab’s success is due to lessons learned from Liedotke’s compassion and ability to “see people as more than just scientists.”

“Trying to meet deadlines is a challenge,” Moore said. “Young faculty members have tenures and there is a lot of pressure to deliver results. Yes, we need data, but we will always need it.”

headaches and hormones

Armed with a hunch about the origins of migraine pain, Moore is tackling new scientific challenges. She’s embarking on several new human-focused projects, working with Duke her health doctors (including her own migraine doctor for 15 years).

One of Moore’s recent grant applications with a pediatric neurologist at Duke University Klaus Werner, M.D.and Dr. Timothy A. CollinsHead of Headache and Pain in Neurology, he aims to improve treatment for teens with “headaches that last almost every day.”

Moore is also researching trigeminal neuralgia (trigeminal neuralgia), which has the eerie nickname of “suicide disease.” Trigeminal neuralgia is a chronic pain disorder that causes excruciating pain in the face. He is also investigating the relationship between migraines and eye stroke. Ignoring it will reduce your vision.

Of most interest to her is a new project investigating why 2 in 3 women with migraines report cycle-related migraines.

“In our lab, we set out to study the role of sex hormones such as progesterone, estrogen and even testosterone at a fundamental level in regulating TRP channels,” said Moore. “My hypothesis is that sex hormones are involved in the inhibition of TRP channel signaling just before the onset of menstruation. It leads to pain.” Further experiments are needed to test this and other hypotheses.

Moore is busy, to say the least, despite continuing to endure migraines.

She calls herself a “functional migraine sufferer.” She has a migraine and she can’t sit still. Her pain worsens when the computer monitor is bright. To cope with this, she’s often busy in her lab, slowly working towards a better migraine cure, as she navigates herself through the next wave of throbbing head pains.

Dr. Dan Vahaba is Director of Communications at the Duke Institute for Brain Science.

Photo by Jim Rogalski, Senior Video and Multimedia Producer, Office of Strategic Communications, Duke University School of Medicine.

Main photo: Dr. Carlene Moore is an assistant professor of neurology at Duke University School of Medicine, studying pain from sunburns to migraines.