Mass General Brigham Researchers Launch New Effort to Find Treatments for Chronic Pain and Migraine

Together with Boston Children’s, Mass General Brigham investigators aim to combine strong pain medicine, surgery, and pathology programs with state-of-the-art, single-cell technologies to pinpoint the human cells and molecules that drive chronic pain and migraine.

Chronic pain and headache disorders affect tens of millions of people in the U.S. each year. New and effective treatments have been slow to emerge despite advances in basic and preclinical research. One reason for this is that human cells and tissues from patients with chronic pain have been difficult to obtain and study. A cross-institutional team from Mass General Brigham’s founding members, Brigham and Women’s Hospital (BWH) and Massachusetts General Hospital (MGH), and from Boston Children’s Hospital, seeks to change that. Led by principal investigator William Renthal, MD, PhD, of the Brigham’s Department of Neurology, the group has received a $13 million grant from the National Institutes of Health to establish the Harvard Human PRECISION Pain Center. This new center will collect human samples related to chronic pain and study them at unprecedented molecular genetic detail to find new therapeutic targets.

“Our goal is to help patients by starting with patients — samples from people who are experiencing or have experienced chronic pain or headache disorders may help us to identify new and specific treatment targets,” said Renthal, who is also the director of research at the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital. “By collaborating across clinical and research specialties, we will be able to collect patient samples. In some situations, these are surgical samples that would otherwise be discarded, but for us, these samples are precious. They may hold critical clues that could help us understand what’s driving chronic pain.”

While preclinical studies have contributed to our understanding of chronic pain, the Harvard Human PRECISION Pain Center aims to overcome many of the inherent limitations of animal models that have made it difficult to translate these findings into new treatments. Today, single-cell genomic tools allow researchers to study molecular changes that occur in distinct cell types of patients with a history of chronic pain. The team plans to use these tools to identify the molecular, structural, and physiological features of human nociceptors, the neurons responsible for detecting and transmitting pain signals to the brain, and define how these are modified in pathological conditions. Their goal is to find non-opioid treatments that can resolve pain without leading to addiction.

The multi-investigator award includes co-principal investigator Clifford Woolf, MD, PhD, of Boston Children’s Hospital, a pain researcher who has pioneered efforts to study pain and sensitivity around injury sites. Renthal and Woolf have teamed up with Jochen Lennerz, MD, PhD, Associate Chief of Pathology at MGH, and Kyle Eberlin, MD, Harvard Plastic Surgery Residency Program Director and Hand/Peripheral Nerve Surgeon in the MGH Department of Surgery. Lennerz will direct the Center’s efforts to collect high-quality autopsy tissue samples while Eberlin will direct the collection of samples from patients undergoing surgery to treat symptomatic neuroma, a painful condition related to neuropathic and phantom limb pain and caused by the disorganized nerve regeneration and recruitment of immune cells following injury. Additional collaborators include Brian Wainger, MD, PhD, a pain specialist at MGH, who will lead studies involving human neuron physiology; Jeffrey Moffitt, PhD, of Boston Children’s Hospital, who will lead the Center’s spatial biology program; and Xianjun Dong, PhD, Director of the Bioinformatics Hub at BWH, who will lead the Center’s Data Core.

“We envision that bringing together the tools of genomics, clinical samples from patients, and expertise from across our academic medical centers will lead to insights that may help us prioritize new pain therapeutic targets,” said Renthal.

More details about the work can be found on the Harvard Human PRECISION Pain Center's website.