Diabetes Drug Shows Promise for Chronic Pain

Editors’ Note: This feature appears as it was published in the summer 2019 edition of UT Dallas Magazine. Titles or faculty members listed may have changed since that time.
Left to right: Dr. Sven Kroener, Stephanie Shiers and Dr. Ted Price BS’97


Scientists seeking an effective treatment for one type of chronic pain believe a ubiquitous, generic diabetes medication might solve both the discomfort and the mental deficits that go with the pain.
“People who are in constant pain have problems thinking straight sometimes. The longer you’re in pain, the more entrenched the impairment becomes,” said Stephanie Shiers, a cognition and neuroscience doctoral student at UT Dallas and lead author of the cover article in the Aug. 15, 2018, issue of the Journal of Neuroscience. “These impairments aren’t addressed by existing therapeutics.”
In the study, UT Dallas researchers show how a type of chronic pain called neuropathic pain responds to metformin, one of the most prescribed medications worldwide, as well as to pain relievers gabapentin and clonidine.
Neuropathic pain is caused by damage to nerve cells. Examples include phantom limb syndrome, pain resulting from a stroke and the “pins and needles” sensations associated with diabetes.
Dr. Sven Kroener, associate professor, and Dr. Ted Price BS’97, a Eugene McDermott Professor, both in the School of Behavioral and Brain Sciences, are co-senior authors of the paper. Price, who is head of neuroscience, explained that pain affects a wide variety of regions of the brain.
“The sensory input that drives pain sends electrochemical signals almost everywhere in your brain, including the prefrontal cortex,” Price said. “When neuropathic pain occurs and certain nerves become active all the time, a huge swath of your brain is now receiving this constant sensory input, and it has to adapt. It makes it go haywire.”
The study, which was conducted on mice, used a task that gauges attention and mental flexibility to measure how each drug helped or harmed the cognitive abilities of the rodents.
While clonidine did not change task performance and gabapentin affected it negatively, metformin reversed pain-induced impairments.
“We chose clonidine because it has a very robust effect on pain if injected into the spinal canal, and gabapentin because that’s the most widely prescribed non-narcotic pain drug,” Shiers said.
Previous studies have established that neuropathic pain patients’ cognitive deficits can persist even when the pain has been treated.
“That suggested to us that there was a long-lasting type of structural change at work in the brain,” Shiers said. “In this regard, metformin outperformed both clonidine and gabapentin.”
Kroener, whose research focuses on the function of the prefrontal cortex in animal models of schizophrenia and addiction, said the next step is to gain a better understanding of why metformin is effective in these cases.
“It’s great if a drug works. It’s even better if we know how it works,” Kroener said. “We observe the results, but we don’t know how they are achieved. That’s what we should pursue next: determining the pathways in which metformin works to correct these defects and how the physiology changes.”
Their work was supported by the National Institutes of Health and the UT System STARs (Science and Technology Acquisition and Retention) program.