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Study shows protein relieves pain hypersensitivity in preclinical models

MD Anderson Research News October 21, 2025

• Scientists find new role for LRRC8A protein in regulating pain
• Increasing LRRC8A expression reduced pain hypersensitivity in preclinical models of nerve injury-induced chronic pain
• LRRC8A could be a potential target for controlling pain in those who experience chronic pain due to cancer treatments or nerve injuries 

According to new research from Â鶹ӳ»­ MD Anderson Cancer Center, a specific protein called LRRC8A in sensory neurons inhibits pain hypersensitivity, highlighting a potential therapeutic strategy for nerve pain. The study, published today in , was led by , professor of Anesthesiology and Perioperative Medicine.

¡°Our research reveals that nerve damage boosts NMDA receptor activity and amplifies pain signaling by lowering LRRC8A, a protein that normally keeps NMDA receptor activity in check,¡± Pan said. ¡°Using gene therapy to restore LRRC8A levels eliminates this receptor hyperactivity and relieves neuropathic pain.¡±

Why is it important to study nerve pain in connection with cancer?

Many patients undergoing cancer treatments experience damage or dysfunction of the nerves, leading to debilitating chronic nerve pain. Unfortunately, these patients have limited options because nerve pain responds poorly to current medications.

Certain receptors called NMDARs  are known to increase pain transmission in the spinal cord. NMDARs usually are inactive, but they can become overactive after surgery, nerve injury, tumor invasion or chemotherapy, leading to increased pain sensitivity. Understanding the mechanisms that regulate NMDARs to avoid hypersensitivity can help lead to treatments for nerve pain.

What do these findings mean for patients who experience chronic nerve pain?

The researchers showed that the LRRC8A protein binds with and restrains NMDARs in the spinal cord. They also demonstrated that nerve injury lowered the expression of LRRC8A in preclinical models, increasing NMDAR activity.

Increasing LRRC8A expression in the spinal cord eliminated NMDAR hyperactivity in lab models of nerve injury, suggesting that this approach would be helpful for patients with chronic nerve pain due to cancer treatments.  

Overall, these findings identify an important new role for LRRC8A in regulating pain hypersensitivity in the spinal cord, highlighting a potential therapeutic strategy to develop more personalized treatments. 

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For a full list of collaborating authors, disclosure and funding sources, read the full paper in .