Deep inside the brain, a small group of nerve cells helps control how strongly pain signals are felt. Under normal conditions, this system can suppress pain traveling through the spinal cord. After nerve damage, however, the same circuitry can become overactive and help sustain chronic pain.
Researchers at Washington University School of Medicine in St. Louis have now identified a mechanism that helps explain this switch and may offer a way to reverse it. In mice, they found that receptors on cells in the brain's main alert and stress center can act as biological brakes that restrain pain. These receptors were already known for their role in stress, but the new findings suggest they can also quiet a pain-producing circuit and reduce chronic neuropathic pain caused by nerve injury.
The study, published Aug. 17 in Current Biology, points to the locus coeruleus as a possible target for future pain therapies designed to act more precisely within the brain.
"Millions of adults live with chronic neuropathic pain caused by nerve damage," said Jordan McCall, PhD, an associate professor in the Center for Clinical Pharmacology in the WashU Medicine Department of Anesthesiology and the study's senior author. "The pain is difficult to treat, and traditional opioid medications bind to receptors throughout the entire body and brain, often leading to side effects, tolerance and addiction risk. Understanding how localized receptors in the locus coeruleus act as gatekeepers could lead to more targeted, effective pain therapies with fewer risks."
