More than 20 million people in the United States live with neuropathic pain—a kind of long-lasting and hard-to-treat nerve pain.
For about one in four of these people, the pain falls into a special category called cryptogenic sensory polyneuropathy, or CSPN. The word “cryptogenic” means the cause is unknown. That’s what makes CSPN so frustrating for patients and doctors alike.
When doctors don’t know what’s causing the pain, it’s hard to know which treatments will work best. Many people with CSPN try different drugs to ease their pain, but there hasn’t been clear guidance on which medicine works best. That’s why a recent study by researchers at the University of Missouri is such an important step forward.
The researchers wanted to find out which of four common drugs worked best for people with CSPN. They included 402 patients aged 30 or older who had been diagnosed with the condition and had moderate to severe pain. These people were randomly placed into four groups, each group taking a different drug for 12 weeks.
The four medications tested were:
Nortriptyline, an older antidepressant
Duloxetine, a drug that affects brain chemicals like serotonin and norepinephrine
Pregabalin, often used to treat seizures or nerve pain
Mexiletine, usually used to treat heart rhythm problems
Every few weeks, the researchers checked in with the participants to see how well their pain was controlled and how many had stopped taking the medication due to side effects or other problems.
The results were clear: nortriptyline worked best overall. About 25% of the people who took it said their pain got much better. It also had the second-lowest dropout rate, meaning most people could keep taking it without too many issues. Duloxetine was a close second, with 23% of patients feeling better and the lowest dropout rate of 37%.
Pregabalin did not work as well, helping only 15% of participants. And mexiletine had the worst results: a high dropout rate of 58%, making it the least helpful drug overall.
Although none of the drugs worked for everyone, the study suggests that nortriptyline and duloxetine are the best choices to try first when treating CSPN. They offer a good balance of pain relief and fewer side effects, making them more tolerable for long-term use.
The study also pointed to other non-opioid medications, like gabapentin and venlafaxine, which are sometimes used for similar nerve conditions. The researchers believe these drugs should be studied next to give doctors even more tools for treating nerve pain.
This research gives hope to many people who suffer from ongoing, unexplained nerve pain. For patients and doctors, it offers much-needed guidance on where to start when looking for relief. By focusing on both how well the drugs work and how easy they are to take, the study helps improve treatment decisions for a very difficult condition.
If you care about pain, please read studies about how to manage your back pain, and Krill oil could improve muscle health in older people.
For more health information, please see recent studies about how to live pain-free with arthritis, and results showing common native American plant may help reduce diarrhea and pain.
The study was led by Dr. Richard Barohn and was published in JAMA Neurology.
Copyright © 2025 Knowridge Science Report. All rights reserved.
