Researchers Ready to Try Deep Brain Stimulation to Reduce Pain in Spinal Cord Injured Patients

Inspired by Hentall’s preclinical research and powered by a three-year $750,000 grant from the U.S. Department of Defense, Hentall, Jagid and their collaborators at The Miami Project to Cure Paralysis and the Miami VA Healthcare System will test the safety and efficacy of using deep brain stimulation in spinal cord injured patients to reduce pain and episodes of high blood pressure called autonomic dysreflexia, and improve function. Already used to control some of the most disabling symptoms in Parkinson’s patients and related movement disorders, deep brain stimulation involves implanting a “brain pacemaker” in the body that transmits electrical pulses to a specific region of the brain to alter its activity.

“One of the things that makes this Phase I clinical trial so promising is that we will use a well- established method, which is deep brain stimulation for Parkinson’s disease, and apply it to spinal cord injury,” Hentall said. “In other words, we don’t have to invent a new device. If this works, we can translate it to the clinical setting relatively quickly. It is not a cure, but it may well ease the pain spinal cord injury patients feel, and could even benefit some of their other symptoms.”

The military’s interest in exploring that hope for active-duty personnel or veterans who suffer spinal cord injuries comes from Hentall’s preclinical research at The Miami Project, as well as advances in the growing field of deep brain stimulation. Hentall already has demonstrated in animal models that stimulating the periaqueductal gray, the midbrain region of the brain that releases pain-relieving molecules, for a few weeks after spinal cord injury reduces sensitivity to pain, improves food transit to the stomach and intestines, normalizes insulin levels, reduces the development of autonomic dysreflexia and enhances movement.

The reduction in pain sensitivity, Hentall says, as well as the other benefits of deep brain stimulation, are likely a result of alterations in various cellular signaling pathways that enhance growth in the damaged spinal cord. As a result, he believes that deep brain simulation will not only suppress pain related to spinal cord injury (SCI), but enhance the pathway that promotes repair. He and his research team, Melissa Carballosa Gonzalez, Ph.D., assistant scientist, Catalina Martinez, M.S., research associate, and Alberto Vitores, B.S., research associate, already have found that this brain pathway increases a key repair molecule, cyclic adenosine monophosphate (cAMP), in the injured spinal cord.

In addition to Jagid, who has many years of experience with deep brain stimulation (DBS) surgery and technology, Hentall’s trial collaborators include Bruno Gallo, M.D., assistant professor of neurology, who is an expert at fine-tuning deep-brain stimulators for individual patients; Eva Widerström-Noga, D.D.S., Ph.D., research associate professor of neurological surgery in the Rehabilitation Medicine and Neuroscience Program, and Health Scientist at the VA, who is an expert in SCI-induced pain, and Alberto Martinez-Arizala, M.D., associate professor of neurology, orthopaedics and rehabilitation, who heads the SCI Clinic at the VA.

The team already has obtained approval from the Food and Drug Administration to use the Medtronic Activa PC DBS device in up to 12 spinal cord injured patients, and is awaiting approval from the VA’s internal review board to begin enrolling them. UM’s review panel already has approved.

Surgically implanted under the skin near the collarbone, and connected to an electrode that is threaded into the brain, DBS devices are now helping more than 100,000 Parkinson’s patients. The devices also have been used in clinical trials to stimulate the periaqueductal gray region of a few hundred patients with treatment-resistant chronic pain. Approximately 40 of those individuals had a spinal cord injury.

The results of those trials, Hentall said, have been variable because they were conducted differently, using various stimulation patterns and targets, injury types, pain symptoms, and durations of follow-up. As a result, the question of whether deep brain simulation can effectively reduce spinal cord injury-induced pain remains unanswered. Moreover, nobody has looked at the permanent benefits of this stimulation after spinal cord injury, or at symptoms other than pain.

Hentall, Jagid and the rest of their team are eager to begin answering those questions.

“Deep brain stimulation has proven to be a highly effective way to improve quality of life in those suffering with neurodegenerative disorders,” Jagid said. “The ability to deliver this therapy in a minimally invasive way, its low complication rates, and its fully reversible effects make it a perfect match for those living with spinal cord injury. We are optimistic about its potential to significantly improve the pain they experience and, therefore, improve their quality of life.”

University of Miami