Harnessing the Anti-Inflammatory Power of Stem Cells to Reverse and Prevent Opioid Tolerance


Promising new research from the lab of Jianguo Cheng, MD, PhD, Department of Neurosciences, Lerner Research Institute, and Department of Pain Management, Anesthesiology Institute, shows that stem cells can prevent and reverse opioid tolerance and opioid-induced pain sensitivity in two preclinical models. These findings may have important implications for the opioid epidemic sweeping across the United States.

Opioid tolerance (OT) and opioid-induced hyperalgesia (OIH)—or increased sensitivity to pain—are two major challenges associated with opioid therapy, and often predispose people to opioid addiction. Mediated by independent cellular pathways, OT, OIH and neuropathic pain are all associated with neuroinflammation. Mesenchymal stem cells (MSCs) are known to have anti-inflammatory effects and are used to treat many diseases and conditions. Dr. Cheng and his team set out to investigate whether they may also confer benefits for pain management and opioid, specifically morphine, therapy.

To test whether MSCs could reverse OT and OIH, the researchers administered MSCs to animal models with established OT and OIH that received daily morphine injections. A single MSC treatment significantly restored the animals' sensitivity to morphine and effectively and rapidly reversed OIH by about 70 to 80 percent. To test whether MSCs could prevent OT and OIH, the researchers administered MSCs to animal models without established OT and OIH and then gave them daily doses of morphine. A one-time MSC treatment prevented the development of OT for the entire duration of the study and substantially reduced the development of OIH. Taken together, these results suggest that MSCs have positive preventive and therapeutic effects on OT and OIH.

These benefits may be modulated by immune cells and glia cells, which surround and provide support for neurons. Protein analyses suggest that MSCs stimulate paracrine release of important mediators, including transforming growth factor (TGF), interleukin 10 (IL-10) and leukemia inhibitory factor (LIF), which regulate these cells. More research is needed to investigate these mechanisms and MSCs' effect in humans, but Dr. Cheng says this preliminary research is very positive and has enormous potential to improve opioid efficacy and safety in clinical practice.

For more information about the study and what it may mean for the opioid crisis, watch Dr. Cheng's interview with News 5 Cleveland or listen to his podcast interview with Akron radio station WAKR.

Dr. Cheng is Professor of Anesthesiology at Cleveland Clinic Lerner College of Medicine and Director of Cleveland Clinic's Multidisciplinary Pain Medicine Fellowship Program. He is also President-elect of the American Academy of Pain Medicine.