Jürgen Sandkühler, a neurophysiologist at the Center for Brain Research of the Medical University of Vienna, and a co-author of the paper, told Nature the original painful stimulus — such as an injury or surgery — changes how the central nervous system handles pain over time and causes long-term potentiation, where nerves fire pain signals repeatedly.
The team induced long-term potentiation in rats by exposing nerve fibers known to carry pain signals to low-frequency electrical stimulation, exposing them to high-frequency electrical stimulation or injecting capsaicin, the pain-causing ingredient in chili peppers.
Researchers gave the rats a high intravenous dose of remifentanil — up to four times the dose usually given to control pain. The drug reduced the pain within 10 minutes, but even after the drug’s effects had worn off, the chronic pain was significantly reduced in the rats treated with low-frequency stimulation. A second dose given an hour later returned the pain levels to normal.
Although the dose is high, it’s well below the fatal threshold, Dr. Sandkühler says. In pre-clinical trials, patients tolerated the dosage well.
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