More than 20 million people in the United States live with neuropathic pain, a type of chronic pain caused by damaged or malfunctioning nerves. In about a quarter of these cases, doctors can’t figure out what’s causing the pain.
This condition is known as cryptogenic sensory polyneuropathy, or CSPN. “Cryptogenic” means the cause is unknown, which makes CSPN especially hard to treat.
When doctors don’t know what’s causing nerve pain, it becomes difficult to decide which medications will work best. There is limited guidance available for treating CSPN, so patients often try different drugs before finding one that helps—or they may find that nothing works well at all.
To better understand which medications might be most helpful, researchers from the University of Missouri carried out a large study. They looked at four drugs that are already used to treat nerve pain and compared how well they worked for people with CSPN.
The study involved 402 adults, all aged 30 or older, who were living with serious nerve pain. Each participant rated their pain at a level of 4 or higher on a 10-point scale, showing they were dealing with significant discomfort.
Each person was randomly given one of four medications: nortriptyline, duloxetine, pregabalin, or mexiletine. These drugs are all used to treat pain, but they work in different ways. Nortriptyline is an older antidepressant that is sometimes used for nerve pain.
Duloxetine is also an antidepressant, but it belongs to a newer group called SNRIs, which affect certain chemicals in the brain. Pregabalin is usually used to prevent seizures and treat nerve pain, while mexiletine is more commonly used to control irregular heartbeats but can also be prescribed for pain.
The patients took their medication for 12 weeks, during which doctors measured how much their pain improved and whether they continued the treatment or stopped due to side effects or lack of benefit.
By the end of the study, nortriptyline was the most successful medication overall. About 25% of patients taking nortriptyline felt real relief from their pain. It also had a relatively low dropout rate—only 38% of patients stopped taking it. Duloxetine was close behind, with 23% of patients finding it helpful and just 37% stopping the drug.
Pregabalin had the lowest success rate, helping only 15% of patients, while mexiletine had the highest quit rate—more than half the patients (58%) stopped taking it, possibly because of side effects or lack of improvement.
While none of the drugs were a perfect solution, the results suggest that nortriptyline and duloxetine might be the best starting points for people with CSPN. These two medications offered the best balance of pain relief and patient tolerance.
Other medications—like gabapentin, venlafaxine, and some sodium channel blockers—are also used to treat nerve pain. The researchers say that future studies should look at these options, too, so that doctors can have a clearer idea of which treatments are most likely to work.
This research is an important step toward helping people who live with unexplained nerve pain. By identifying which medications offer the most promise, doctors may be able to give their patients faster, more effective relief. The study was published in JAMA Neurology and led by Dr. Richard Barohn and his team.
As more studies are done, patients and doctors can look forward to better guidance and treatment options for this challenging condition.
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