Back Pain Traced to Unique Cell Subtype in Spinal Discs

In a significant breakthrough, a recent study conducted by Cedars-Sinai may have unravelled the mystery behind a specific type of back pain that afflicts nearly 40% of the adult population. The research focuses on understanding the mechanisms that lead to pain in degenerating intervertebral disks in the spine, a common cause of low back pain.

Although this ailment has been widely experienced, the exact reasons for the disks becoming painful have remained elusive in the realm of medical science. However, the recent study, published in the journal Science Translational Medicine, offers a promising avenue for both understanding and potentially treating this prevalent condition. 

Dmitriy Sheyn, Ph.D., a research scientist in the Board of Governors Regenerative Medicine Institute at Cedars-Sinai and the senior author of the study, expressed the significance of their findings. “We’ve identified for the first time particular cells that could be the key to understanding disk pain,” he stated. “Learning more about how these cells work could lead to the eventual discovery of new treatment options.” 

The spine consists of bones separated by jelly-filled spacers known as intervertebral disks, serving as shock absorbers. Over time, due to factors such as age, overuse, or injury, the jelly within these disks starts to dry out and degenerate. However, not all degenerated disks necessarily cause pain. Sheyn explained, “This is because the inner jelly-like layers of the disks contain no nerve endings. But sometimes, when disks degenerate, nerve endings from the surrounding tissues invade the disk, and we believe this causes pain.” 

The study delves into the various cell types within the jelly-like layer of intervertebral disks. By comparing cells from patients with pain-free degenerated disks to those from patients experiencing disk-associated low back pain, researchers discovered that the latter group had a higher abundance of a specific subtype of cell potentially implicated in the onset of pain. 

Hyun Bae, MD, professor of Surgery and Orthopaedics at Cedars-Sinai and a co-author of the study, emphasized the breakthrough in understanding disk-associated back pain. “This is an essential step toward finding a nonsurgical biologic treatment,” he noted, hinting at the potential for novel therapeutic approaches. 

Mark Vrahas, MD, chair of Cedars-Sinai Orthopaedics, underscored the importance of the discovery in reshaping back pain management. “Unveiling the key cells behind disk-related pain marks a pivotal stride in reshaping how we approach back pain management,” he stated. “This discovery opens doors to targeted therapies that may revolutionize orthopedic treatments, offering hope to millions worldwide.” 

The researchers conducted experiments where healthy cells were subjected to conditions mimicking disk degeneration in a cell culture dish. These conditions included inflammation, acidity, tension and compression, low glucose, and low oxygen. Remarkably, the healthy cells transformed into the pain-associated subtype under these simulated degenerative conditions. 

Furthermore, investigators employed a specialized two-chamber laboratory chip, growing cells in one chamber and introducing pain-signaling neurons created from stem cells in the other. When pain-associated cells were present in the chip, pain-signaling neurons extended axons (special fibers nerves use to transmit information) toward them. Conversely, when healthy cells were in the chamber, the neurons did not send out axons. 

Dmitriy Sheyn highlighted the significance of this observation, stating, “We don’t know whether the pain-associated cells attracted the invasion of the neurons, or the healthy cells repelled it, but there was definitely a difference between the healthy and the pain-associated cells.” 

In terms of future treatments, the newfound information suggests the possibility of reprogramming pain-associated intervertebral disk cells into healthy cells or introducing healthy cells to painful disks to overpower the pain-associated cells. Clive Svendsen, Ph.D., executive director of the Board of Governors Regenerative Medicine Institute at Cedars-Sinai, emphasized the potential for targeted cell therapy.

“Precisely targeting the ‘bad’ cell subtype or supplementing the ‘good’ cell subtype may provide useful strategies for treating disk-based low back pain,” Svendsen explained. “This study validated some knowledge in classical disk or pain biology and could be a step toward a targeted cell therapy that addresses the root causes of low back pain.” 

Journal Reference  

Wensen Jiang et al, Intervertebral disc human nucleus pulposus cells associated with back pain trigger neurite outgrowth in vitro and pain behaviors in rats, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.adg7020.