Old Cancer Drug May Have New Purpose Treating Chronic Pain
/By Pat Anson, PNN Editor
Over the years, several drugs that were developed to treat medical conditions such as epilepsy and depression have been repurposed as treatments for chronic pain — often with mixed results. Pregabalin (Lyrica) and duloxetine (Cymbalta) are just two examples.
A team of researchers at Duke University may have found a new pain medication while looking through what they call the “junkyard of cancer drugs.” They analyzed over 1,000 compounds contained in Compound Libraries at the National Cancer Institute, looking for drugs that reset genetic switches that control neurotransmission. Their goal was to find a drug that doesn’t just temporarily block pain signals, but changes the underlying mechanism that causes pain sensation.
“Because chronic pain, like many chronic diseases, has an important root in genetic switches being reprogrammed in a bad way, a disease modifying treatment for chronic pain should reset the genetic switches, not just cover up the pain, as with opioid and aspirin/Tylenol-like painkillers." said Wolfgang Liedtke, MD, an adjunct professor of neurobiology at Duke and an executive scientist at Regeneron Pharmaceuticals.
Liedtke and his colleagues identified four promising compounds. Among them was kenpaullone, a drug developed over 20 years ago that inhibits neurotransmission by activating a gene called Kcc2. When Kcc2 is enhanced, it reduces chloride levels in nerve cells and silences pain signals.
In laboratory mice, Liedtke's team found that kenpaullone significantly reduced pain caused by nerve injury and bone cancer. The pain relief was long-lasting, which is consistent with the drug stopping pain signals through gene regulation.
"At this stage, we knew we had met the basic requirement of our screen of shelved cancer drugs, namely identified Kcc2 gene expression-enhancers, and demonstrated that they are analgesics in valid preclinical pain models,” Liedtke explained in a university press release.
Encouraged by their findings, Liedtke's team assessed whether kenpaullone affects spinal cord processing of pain and whether kenpaullone treatment can reduce chloride levels in pain-relaying neurons. Both sets of experiments on laboratory mice produced positive results.
The research findings, published in the journal Nature Communications, suggest that kenpaullone and gene therapy both have the potential to become treatments for chronic refractory pain conditions, such as neuropathy, cancer bone pain, trigeminal neuralgia, and other forms of chronic pain associated with poor Kcc2 function.
Controlling pain through experimental gene therapy is in its early stages, but has produced some intriguing results. In a study earlier this year, researchers at the University of California San Diego used a gene editing tool to alter a gene that senses pain in mice. The suppressed gene increased pain tolerance, lowered pain sensitivity and provided months of pain relief without the use of drugs.
