Painful Brakes

Like a mis-wired fire alarm continuously blaring after the smoke has cleared, neuropathic pain can linger for months or years after an injury appears fully recovered because nerves and pain pathways are damaged. New research suggests a failure to keep immune genes under control inside damaged sensory neurons may contribute to this problem. A protein called ZFP612 (blue, with its corresponding genetic material in pink, pictured in green mouse neurons) normally acts as a brake by silencing the immune receptor gene Il1rl1, but in injured sensory neurons ZFP612 levels drop. With the brake released, Il1rl1 is activated, triggering signalling that causes chronic pain hypersensitivity. The study found that silencing ZFP612 in healthy mice caused pain hypersensitivity, and conversely, restoring it in injured mice reduced pain. And, if Il1rl1 was removed, silencing ZFP612 no longer caused pain. Targeting this pathway could bring much-needed relief to patients with chronic pain.

Written by Anthony Lewis

Anthony Lewis

Writer

Ant was the web editor in the early days of BPoD, and has since worked with the UK’s top science organisations as a writer and multimedia producer. He now splits his time between freelance work and managing multimedia at The Lancet.

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• Image from work by Longfei Ma 马龙飞, Yangyuxin Huang, Meiling Han, Bing Wang and Xinying Guo, and colleagues
• Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
• Image originally published with a Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)
• Published in Nature Communications, November 2025