A multidisciplinary group of scientists and clinicians at the University of Minnesota is studying trigeminal neuralgia (TN), otherwise known as the “suicide disease.” The condition causes acute, chronic pain to arise along the trigeminal nerve, the largest of the cranial nerves, which is responsible for sensation in the face and mouth.

The group of researchers includes:

  • Andrew Grande, MD, and Sean Moen, Department of Neurosurgery
  • Bharathi Jagadeesan, MD, Department of Radiology
  • Donald Nixdorf, DDS, MS, School of Dentistry
  • Pierre-Francois Van de Moortele, MD, PhD, Center for Magnetic Resonance Research (CMMR)
  • Kellen Mulford, PhD candidate.

“Since 2012, we’ve been amassing MRI images of my TN patients’ trigeminal nerves,” explained Grande. “Our goal is to try and understand the pathophysiology of trigeminal neuralgia – why it occurs. We’re starting with an anatomic view, taking advantage of high-resolution MRIs available through the CMMR.”

Differing perspectives
The researchers are looking at trigeminal neuralgia from several different angles. “One is related to radio frequency rhizotomies done to treat the condition,” Grande explained. “We burn the nerve to help eliminate the pain. What we’ve never done is correlate the area of the burn, or lesion, to the three anatomic divisions of the trigeminal nerve.”

Why is that important? “If the nerve regrows and the pain comes back, I’d be inclined to go back and repeat the procedure,” explained Grande. “If the pain comes back without nerve regrowth, we need to start speculating about why and whether another lesion is the right thing to do.”

The researchers are corelating the imaging work with anatomic dissections from the U’s Neuroanatomy Lab. “We have several dissections of the trigeminal ganglion and want to compare those to the fiber tracts we see on the MRIs,” said Grande. The advantage of having the dissections is that MRIs are often not sensitive enough to see all the tracts. “This will enable us to see if the lesions are stable or if they go away.”

Visitor from Johns Hopkins
The group recently hosted a visiting scientist from Johns Hopkins Medicine in Baltimore, MD. “Most specialists don’t feel comfortable treating facial pain patients,” said Tina Doshi, MD, assistant professor of Anesthesiology and Critical Care Medicine. “I was the same. I’m a board-certified, fellowship-trained pain management physician and yet during my anesthesia training and even my pain management training, I got very little exposure to facial pain. I wasn’t really taught it in any systematic way.” During a postdoctoral research fellowship, however, Doshi began studying biomarkers in patients with TN, and developed an interest in treating a variety of craniofacial pain disorders.

Then Doshi met Nixdorf, who told her about the multidisciplinary group studying and treating trigeminal neuralgia at the U of M. “I thought it sounded fantastic,” she said. “Don invited me to come out and look at how they assess their facial pain patients, what things they do for them and learn a little bit more about good ways to approach these really challenging patients.”

“As a dentist, I have focused on the face my entire career, which gives me a unique perspective from which to contribute,” Nixdorf said. “Collaborating with others, such as Tina, to improve patient care outcomes is the best path forward. But it is not easy and does not exist at many institutions when it comes to diagnosing and treating patients with TN and facial pain.”

U of M legends in the field
While on campus, Doshi spent time observing in the Facial Pain Clinic and met with facial pain researchers, George Wilcox, PhD, Professor, Department of Neuroscience, and Don Simone, PhD, Professor, Chair, Department of Diagnostic and Biological Sciences. “They are legends in the field of pain neurobiology,” Doshi said. “I also met with collaborators in the Departments of Biomedical Engineering, Medical Physics, and Radiology…it truly was a multidisciplinary group, which is important for both pain treatment and pain research.”

The goal of Doshi’s visit was to work with Nixdorf and other U of M scientists and clinical pain specialists on several collaborative projects. “I can't tell you how valuable my visit to Minnesota continues to be,” she said. “Facial pain now comprises about 50 to 75 percent of my new consults, and it is incredible how many patients I see with TMD [temporomandibular disorders] who have been misdiagnosed. It's been so gratifying to see these patients improve with the right diagnosis and treatment.”

Patients with facial pain caused by trigeminal neuralgia understand how challenging it is to get their condition treated. “People who are experts in this field know it’s not very well taught in many of the contexts within which we see these patients,” Doshi explained. “As clinicians, we need to recognize our own limitations and not be afraid to ask for help from our colleagues in different specialties. Medicine, after all, is a team sport.”

Searching for biomarkers
Doshi’s educational background plus her clinical work and investigations at Johns Hopkins prepared her for the visit. “My postdoctoral training was in clinical trial design and statistics and how to conduct good clinical research,” she said. “I’ve been working on clinical and translational research for trigeminal neuralgia patients, collecting biomarkers for the prediction of outcomes after their treatments.”

“MRI, a non-invasive tool to assess the patient’s brain and nerves, has some of the best promise to identify a biomarker for TN,” added Nixdorf. “Currently, diagnosis is based mostly on patient-related symptoms. While this is acceptable for some patients, for others with overlapping chronic pain conditions and/or who failed to experience reduction in their pain with reasonable treatment approaches, it is problematic because symptoms patients experience change the presentation of their pain and make it difficult to properly diagnosis TN.”

“What we think of as trigeminal neuralgia is actually a spectrum of different disorders,” Doshi continued. “The challenge is to figure out exactly what’s going on with these patients to be able to determine how to treat them. The hope is our research at Johns Hopkins will help identify these biomarkers but if not, give us insights into how to better treat the condition.”

Excited about the potential
Doshi is excited about the growth potential in this area and the work happening at the U of M and Johns Hopkins. “It is a rare condition and we don’t understand it at all,” she said. “We have one FDA-approved medication for treatment, and we have some invasive treatment options, which are variably effective. There is so much left to explore to figure out the mechanisms and treatments for trigeminal neuralgia.”