There’s a mechanism in the brain that researchers have identified that may well become a target for drugs to prevent tolerance to opioid pain medicine, like morphine, according to a study published in the Nature journal Neuropsychopharmacology.
Scientists from Georgia State University and Emory University demonstrated for the first time that morphine tolerance is actually due to an inflammatory response produced in the brain. The inflammation in the brain is caused by the release of cytokines, which are chemical messengers in the body that tell the immune system to act up, resulting in inflammation.
By blocking a particular cytokine, researchers were able to create the same level of pain relief with half the amount of morphine – effectively eliminating opioid tolerance (in rats). That’s correct, equal pain relief with half of the opioids.
This important finding may have critical implications for chronic pain sufferers, who find that because of tolerance to opioid medications, their dosages need to be increased over time, which can lead to less effective pain relief, greater costs, stigma or even the refusal to prescribe or dispense pain medications. By eliminating the tolerance factor, many pain sufferers reliant on opioids for pain relief may see a path towards more effective, compassionate and necessary care.
“These results have important clinical implications for the treatment of pain,” 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.”
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. The problem is that tolerance to morphine, which is defined as a decrease in pain relief over time, significantly impedes treatment for about 60 percent of patients, according to the researchers.
In the absence of pain, morphine interferes with the body’s ability to maintain normal function, which is called homeostasis. When something interferes with homeostasis the body views it as a disease-producing agent, and the body triggers an immune response to rid the body of the agent.
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.
“Our findings provide a novel pharmacological target for the prevention of opioid-induced immune signaling, tolerance, and addiction,” the authors concluded.