Can gabapentin help prevent harmful changes after spinal cord injury?

For years, my research team has been working to understand why a traumatic spinal cord injury (SCI) causes disease and dysfunction in organs throughout the body.

Our latest research, published online in the journal Cell Reports, explores using the widely prescribed pain-relief drug gabapentin in a new way.

We found that gabapentin, when used as a treatment early after injury, can prevent harmful structural changes in the spinal cords of mice and, by blocking these changes, we could also prevent post-injury impairments in function of the cardiovascular and immune systems.

One of my colleagues, Faith Brennan, lead author of the paper and a research scientist in the Department of Neuroscience at Ohio State, led the study exploring the use of gabapentin as preventive therapy after SCI. During this study, our team at The Ohio State University Wexner Medical Center and Ohio State College of Medicine also worked with scientists at Duke University and the University of California San Francisco.

We knew that gabapentin is often prescribed as a treatment for pain for people with a spinal cord injury. In these people, the drug is given many weeks or months after SCI and after patients develop pain. In fact, patients need their doctors to prescribe the medication and only after they seek help do they receive treatment.

But since gabapentin works by binding to molecules in the spinal cord that are important for creating new neuronal circuitry, including the circuits that cause pain and post-injury disturbances in heart rate, blood pressure and immune dysfunction, we asked...”can gabapentin prevent this circuitry from developing in the first place, especially if it is given early after SCI?”

Our thinking was that gabapentin could be used as a pharmacological “sealant” that would inhibit the formation of critical building blocks that cause harmful neuronal circuitry to form in the injured spinal cord.

Our results indicate that the drug can be used in a novel way and, that by treating early after SCI, we can prevent the onset of the harmful structural changes that lead to cardiovascular and immune dysfunction. Equally important, we found that these benefits remain even one month after stopping gabapentin treatment in spinal-injured mice.

Based on these results, we believe that gabapentin could be repurposed as a therapy that can prevent the onset of disease-causing autonomic dysfunction in people affected by spinal cord injuries.

This is the first time a treatment has been shown to prevent the development of autonomic dysfunction after SCI, rather than simply manage the symptoms caused by autonomic dysfunction.

In response to stress or danger, autonomic nerve cells in the spinal cord trigger a ”fight or flight” response. This is a normal and helpful response that increases blood pressure and releases hormones like adrenaline and cortisol.

But after traumatic SCI, massive structural changes occur within spinal autonomic nerve centers that control the fight or flight response, and these changes cause uncontrolled autonomic reflexes.

For example, normally harmless stimuli, such as the bladder filling, will trigger the fight or flight response. But because of the spinal cord injury, the response is uncontrolled and can cause several health problems, including severe high blood pressure, heart rate slowing and long-term damage to the immune system which makes people more likely to develop infections.

Autonomic dysfunction is a major problem for people living with a spinal cord injury. The cardiovascular complications can lead to severe morbidities like heart attack and stroke while long-term immune suppression can lead to serious recurrent infections like pneumonia.

Currently, these symptoms can only be managed, (regular bowel/bladder voiding regimens, for example), but there is no treatment.

The possibility of repurposing gabapentin as a therapy to prevent the development of autonomic dysfunction could significantly improve the quality of life for individuals living with SCIs. This could lead to greater independence in society, reduced caregiver reliance, reduced infection susceptibility and increased life expectancy.

This study builds on previous research at Ohio State’s Neurological Institute and Belford Center for Spinal Cord Injury showing that immune suppression after SCI is caused by autonomic dysfunction.

We don’t know how long gabapentin treatment can be delayed after SCI and still maintain the beneficial effects. Ongoing studies are optimizing this treatment onset window, and we’re also investigating the effects of this therapy on other tissues in the body which may also be affected by SCI.

Phillip Popovich is a professor and chair of Ohio State’s Department of Neuroscience and executive director of the Belford Center for Spinal Cord Injury at The Ohio State University College of Medicine.