Why Opioids Cause Itching: Inflammation, Histamines, and Opioid Side Effects

New Research Identifies the Cellular Receptor Responsible for Triggering Itching Response in Opioid Therapy

Research conducted at University of North Carolina School of Medicine sheds new light on the cause of a frequently encountered side effect of opioid therapy, intense itching. UNC scientists report that the receptor protein MRGRPX2 may be activated to trigger an immune system response that results in itching. The MRGRPX2 receptor exists on the surface of mast cells, and in response to an activation signal, initiates a process called degranulation by releasing histamines and other inflammatory factors, in turn provoking allergic responses that include itching. Co-author Kate Lansu, a graduate student in the lab of Brian Roth, MD, PhD, explained, “Opioid drugs have been link to degranulation also, but it was through an unknown mechanism. We think that our data could potentially explain why degranulation occurs as a side effect of opioid ligands (morphine and other drugs), something that is well-known but not well-understood.” The research is reported in the journal Nature Chemical Biology.

The MRGRPX2 receptor is one of about 120 “orphan” receptors in humans, so-called because of uncertainty about their purpose and function. Dr. Roth’s lab is engaged in the systematic screening of these receptors against many thousands of molecules to determine what activates them. This advance in understanding the itch response mechanism could be useful in the development of receptor antagonists that would reduce the itching side effect of opioid therapy.

A news story about the findings may be read here.

The journal abstract may be read here.

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