Progress in Pain Relief Research, Inspired by the Children
Howard Gutstein, M.D.
About 20 years ago, I started medical practice with no intention of pursuing research.
As the most junior person, I was asked to take care of children with cancer pain. I quickly realized that this was because no one else wanted to do it. The agony that these children endured could be incredible.
Some patients were nearly impossible to treat. In a few cases, children effectively had to be put under general anesthesia to relieve their suffering.
I decided to try and do something more to help these kids. I moved to the University of Michigan and while continuing to take care of children, became a postdoctoral fellow in the research lab of Huda Akil, Ph.D., a noted pain researcher. Many years with her taught me not only research methods, but how to rigorously, creatively, and fearlessly approach even the most daunting scientific problems.
From that time forward, I focused my energies on trying to find more effective ways to relieve pain and suffering. Today, I'm a professor in MD Anderson's Department of Anesthesiology and Perioperative Medicine with an appointment in the Department of Biochemistry and Molecular Biology.
For thousands of years, the most effective treatment for severe pain has been opioid narcotics such as morphine.
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Unfortunately, over time patients develop tolerance to the pain-relieving effects of opioids, and they lose effectiveness. If I could understand what caused morphine tolerance, I would finally be able to treat these patients' pain effectively and alleviate their suffering.
Our recent discovery is a major step toward realizing this dream. We found that the commonly used anti-cancer drug imatinib, known commercially as Gleevec®å, completely eliminated morphine tolerance in rats. It also reversed tolerance in rats that received incredibly high doses of morphine, reflecting the situation we see in many of our cancer patients.
It turned out that morphine tolerance was selectively mediated by an isoform of the platelet-derived growth factor receptor, a known target of Gleevec.
Our study was published online today at Nature Medicine. The animation above illustrates our findings: Morphine connects with its receptor on a brain cell, which causes the cell to express platelet derived growth factors, which then connect to their receptor (PDGFR), causing tolerance to morphine until the process is blocked by Gleevec.
This finding is particularly exciting because Gleevec is already in widespread clinical use, so the lengthy process of translating this discovery to clinical care could be shorter.
I still have nightmares about some of the kids I have taken care of over the years. I hope that they will rest better knowing that their struggles have not been forgotten. I also hope that we will be able to eliminate unbearable pain so the children will know that their suffering was not in vain.
MD Anderson news release
Nature Medicine paper