Breakthrough Study Discovers Mechanism of Morphine Tolerance
New Drug Target Could Prevent Tolerance and Addiction to Opioids, Study Finds
A novel target for pharmaceuticals could help prevent tolerance and addiction to opioid pain medications, such as morphine, according to researchers at Georgia State University and Emory University.
Over 67 percent of the United States population will experience chronic pain at some point in their lives. Morphine is the primary drug used to manage severe and chronic pain, with 3 to 4 percent of adults in the U.S. receiving long-term opioid therapy. However, tolerance to morphine, defined as a decrease in pain relief over time, significantly impedes treatment for approximately 60 percent of the patient population. Long-term treatment with opioids is associated with increased risk of abuse, dependence and dose-related fatal overdose.
This study examined the brain mechanisms behind the development of morphine tolerance. The findings, published in the Nature journal Neuropsychopharmacology in August, show for the first time that morphine tolerance is due to an inflammatory response produced in the brain. This brain inflammation is caused by the release of cytokines, chemical messengers in the body that trigger an immune response, similar to a viral infection. Blocking a particular cytokine could eliminate morphine tolerance.
“These results have important clinical implications for the treatment of pain and also addiction,” said Lori Eidson, lead author and a graduate student in the laboratory of Dr. Anne Murphy in the Neuroscience Institute of Georgia State. “Until now, the precise underlying mechanism for opioid tolerance and its prevention have remained unknown.”
In the absence of pain, morphine interferes with the body’s ability to maintain normal function, referred to as homeostasis. Anything that interferes with homeostasis is viewed by the body as a pathogen, resulting in an immune response to rid the body of the pathogen. When Eidson gave rats drugs that blocked the immune response, the rats no longer became tolerant to morphine.
The study also found that tolerance to morphine develops rapidly. Administering one dose of morphine to rats for three days was sufficient to induce tolerance.
Co-authors of the study include Dr. Anne Murphy of Georgia State and Drs. Kiyoshi Inoue, Larry Young and Malu Tansey of Emory University.
The study was funded by the National Institutes of Health and awards from Georgia State University and Emory University.