Scientists Identify a Brain 'Brake' That Can Shut Down Chronic Nerve Pain

Researchers at Washington University School of Medicine in St. Louis have identified a brain mechanism that can suppress chronic nerve pain in mice, pointing to a possible new way to treat the condition with fewer side effects than current opioid drugs. The findings were published August 17 in the journal Current Biology.

The team, led by Jordan McCall, an associate professor in the university's Department of Anesthesiology, studied the locus coeruleus, a small cluster of brain cells known for its role in the body's alert and stress response, which was already known to help regulate pain. Nerve injury can turn this region from a natural pain suppressor into a source of chronic pain. Neuropathic pain, which produces shooting, stabbing or burning sensations, arises when damaged nerves send abnormal signals to the brain, and it can result from conditions such as diabetes, viral infections and nerve compression.

The researchers found that mu opioid receptors on cells in the locus coeruleus act as a biological brake on this pain circuit. When they removed these receptors from locus coeruleus cells in mice with neuropathic pain, the animals became more sensitive to touch and heat. When the receptors were restored, that heightened sensitivity reversed. Mu opioid receptors are the same receptors that natural and synthetic opioids, including morphine and fentanyl, bind to elsewhere in the brain and spinal cord to reduce pain signalling.

McCall said chronic neuropathic pain affects millions of adults and is difficult to treat because opioid medications act on receptors throughout the entire body and brain, causing side effects, tolerance and addiction risk. The team is now investigating ways to act on the locus coeruleus's pain-suppressing circuitry directly, without engaging opioid receptors elsewhere in the nervous system, in the hope of developing more targeted pain therapies.