Animal Models of Concussion and Post-Traumatic Headache


Frank Porreca, PhD, explains how animal models may be used to improve understanding of pathophysiology of post-traumatic headache and to develop better treatments

In the U.S. each year, there are 1.6 to 3.6 recreational or sports-related concussions. And approximately 29% of people who experience a concussion have long-term effects, which typically includes post-traumatic headache. The American Headache Society defines post-traumatic headache as occurring within seven days of concussion or regaining consciousness after concussion. Symptoms are described as migraine-like and can include pulsing pain, light and noise sensitivity, memory problems, dizziness, and insomnia.

Until recently, there have been very few animal models of concussion and post-traumatic headache. Frank Porreca, PhD, a researcher at the University of Arizona and at the Mayo Clinic, Arizona and member of the International Concussion’s Scientific Advisory Board, is working on one of the first. He recently spoke with us about his research and the benefits of using animal models to better understand concussion and post-traumatic headache.

The Benefits of Animal Models

Dr. Porreca is currently working with researchers at the University of Arizona and Mayo Clinic to identify mechanisms that promote post-traumatic headache and to develop ways to intervene to prevent long-term effects after a concussion including persistent post-traumatic headache.

“We want to know what kind of triggers will be important in precipitating post-traumatic headaches,” he says. “With athletes, for example, they have a traumatic brain injury. Should they return to playing sports, should they have the stress of academic studies, should they exercise, should they stay in a dark room, should they be exposed to light?

While it’s still early to discuss findings, the lab has been able to induce an experimental traumatic brain injury in a mouse. These injuries are similar to concussions that might occur in an athlete’s day-to-day life. The researchers measure the outcomes of the injury, which “can help us to learn mechanisms that we think may be relevant to post-traumatic headache,” Dr. Porreca says.

Over the course of their research, Dr. Porreca and his team have observed changes that occur in terms of the excitability and sensitivity of mice. When inducing the injury in the mice, “there’s no obvious sign of damage to the head of the mouse,” he says. “We’re trying to model the kinds of sports injuries that occur often.”

Following the injury, the team allows the mice to recover and then exposes them to a stressful situation to see if they develop hypersensitivity that might be consistent with the headache phenotype.

How Post-Traumatic Headache Presents in Mice

While there are many benefits to using animal models, there are constraints as well. In addition to measuring the long-term effects of headache, Dr. Porreca is trying to measure pain; however, mice do not convey pain in the same way humans do.

“Post-traumatic headaches present with migraine phenotypes, and so in humans we know that they’re having pain episodes because they tell us,” he says. “Humans are verbal creatures, and animals, of course, are nonverbal. We have to use surrogate measures in order to interpret behavior or outcomes that suggest the animals are in pain.” In order to measure pain more effectively in mice, the researchers are using von Frey filaments that produce touch stimuli that are normally not painful.

“Mice that have been exposed previously to traumatic brain injury become hyper-responsive to these touch stimuli,” Dr. Porreca says. That is interpreted as a pain response, which may be indicative that the animal might be experiencing a post-traumatic headache. Most of the pain responses are seen in and around the head of a mouse, which might be consistent with a headache phenotype.

Research is still ongoing; however, Dr. Porreca hopes to find better treatments and approaches to relieving and eliminating post-traumatic headache in individuals by using animal models to test mechanisms by which therapeutics may be developed.

For more information on concussion signs and symptoms, treatment and diagnosis, visit the International Concussion Society’s resource library.

Frank Porreca, PhD, is a Scientific Advisory Board Member of the International Concussion Society. The International Concussion Society sponsored website Concussion.Org  is the number one destination for information related to concussion prevention, diagnosis and treatment. Our mission is to serve medical professionals, athletes, administrators, coaches, patients and the public by providing a central repository of accurate and scientifically vetted concussion research. Working alongside our world-class scientific advisory board, aims to be the most trusted global index on one of the most common, yet least understood, forms of traumatic brain injury.