UNC researchers link orphan receptor to opioid-induced itching

With a more accurate understanding of the characteristics and function of the receptor MRGRPX2, University of North Carolina School of Medicine researchers were also able to create chemical probe that will allow them study the receptor more precisely.

UNC researchers link orphan receptor to opioid-induced itching click to enlarge Kate Lansu, photo by Max Englund/UNC Health Care

Media contact: Matt Englund, (984) 974-1144, matthew.englund@unchealth.unc.edu

March 24, 2017

CHAPEL HILL, NC – Opioids have long been an important tool in the world of pain management, but the side effects of these drugs – from addiction and respiratory failure to severe itching and dizziness, can be overwhelming. Scientists have been trying to understand how these side effects happen so they can create better, less problematic pain relievers.

New findings published in the journal Nature Chemical Biology by UNC School of Medicine scientists show that MRGRPX2, a receptor protein on the surface of mast cells, can trigger the immune system response that leads to itching associated with some opioids.

Kate Lansu, the paper’s first co-author and a graduate student in the lab of Bryan Roth, MD, PhD, explains how this process works.

“Receptors in mast cells – part of the immune system – respond to an activation signal and release inflammatory factors like histamine, in a process called degranulation,” she said. “When that happens, other cells are recruited to the site of inflammation to clear the infection. This response is also important for things like allergies. And this is what presents itself as itching.”

“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 findings are significant not only because they offer a potential explanation for opioid-induced itching, but also because the data suggest a way to characterize the function of the orphan receptor MRGRPX2.

To read the full article, click here.