Stimulating immune cells could offer new treatment for nerve injury pain

Researchers at The University of Texas MD Anderson Cancer Center have discovered that targeting a specific immune process could help improve recovery after nerve injury and reduce chronic pain.

The study, published in Proceedings of the National Academy of Sciences (PNAS), was led by Peter Grace, Ph.D., associate professor of Symptom Research. The findings reveal that peripheral neuropathy, which can be caused by nerve injury, reduces the ability of macrophage immune cells to clear dead or dying cells – a process called efferocytosis – and leads to chronic pain. Targeting or stimulating efferocytosis could be a viable treatment option.

Chronic neuropathic pain after nerve injury can be debilitating for many patients. We're hopeful that these insights can provide meaningful clinical applications."

Peter Grace, Ph.D., Associate Professor, Symptom Research, University of Texas M. D. Anderson Cancer Center

What is peripheral neuropathy and how do macrophages help?

Peripheral neuropathy – damage to the peripheral nervous system – results in inflammation and chronic neuropathic pain. This condition affects millions of people around the world but remains poorly understood.

Macrophages – certain types of immune cells – prevent inflammation and fix nerve damage using special receptors called MERTK, which recognize the "eat me" signals on dead or dying cells. These macrophages can switch from pro-inflammatory to anti-inflammatory and engulf the dead cells in a process known as efferocytosis. However, it is unclear why this process does not seem to work after peripheral nerve injury.

What did the researchers discover in this study?

The researchers showed that nerve injury releases proteins that remove the MERTK receptor from macrophages, reducing efferocytosis in lab models. This leads to chronic pain, neuronal hyperactivity, nerve and tissue damage and ongoing inflammation. Restoring the ability of macrophages to clear dead cells reduced neuropathic pain and improved tissue repair in these models.

What does this mean for patients with nerve injury?

While these findings are preclinical, they suggest that stimulating efferocytosis is a potential new therapeutic strategy to prevent inflammatory signaling, improve nerve repair and resolve neuropathic pain in patients with nerve injury.

This research is part of MD Anderson's Cancer Neuroscience Program, which is dedicated to uncovering the interactions between cancer and the nervous system to help patients survive and thrive throughout their cancer journey.