Nerve tissue offers insights into chronic neck pain

Chronic neck pain is common and a leading cause of disability. Development of effective treatments has been limited by a lack of understanding of which biological pathways help generate and amplify painful signals in the neck. 

In a molecular study of nerve cells in the upper necks of human patients, researchers were able to link pain with the activity of single cells.  

“By linking human tissue to patients’ pain experiences, we hope to develop treatments that address the cause of persistent neck pain and ultimately improve patients' quality of life,” said one of the paper’s authors, Dr. Michele Curatolo, professor of anesthesiology and pain medicine at the University of Washington School of Medicine. He directs the UW Medicine Interventional Pain Program. 

The findings appeared in the April issue of the journal Brain. 

Pain signals from the neck travel through small bundles of nerve cells called dorsal root ganglia, located just outside the spinal cord. The ganglia at the second cervical vertebra carries signals not only from the neck but also from the back of the head.  

During certain spine surgeries, this upper-spine bundle is sometimes removed as part of routine care. The researchers were able to examine this tissue from 22 spine-surgery patients at UW Medicine to better understand the changes that occur in the cells when pain becomes chronic.  

Half of the patients had recent, short-term neck pain, and half had chronic neck pain lasting three months or longer. 

Using RNA sequencing, the researchers measured which genes were active in individual cells, located those cells within the dorsal root ganglia, and compared patterns between patients with acute versus chronic pain. 

The researchers expected to see major changes in the ganglia’s nerve cells, or neurons, that transmit pain signals. They were surprised to find that the differences between acute and chronic neck pain were not in the nerve cells themselves. 

Instead, major changes were seen in the cells surrounding and interacting with the nerve cells, including endothelial cells, which line the blood vessels, fibroblasts, which organize and support tissue, and Schwann cells, which insulate nerve fibers. 

In patients with chronic neck pain, these non-neural cells showed strong, ongoing inflammation. Many of the more active genes were linked to inflammation, immune signaling, and pain sensitivity.  

This suggests that non-neural cells may send chemical signals to nearby nerve cells, thereby keeping them in a painsensitive state. Consequently, chronic neck pain may be driven by an inflammatory environment around the nerves. 

This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (R01AR078192). 

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