Louis showed that only one opioid receptor isoform is responsible for itching—and it is not involved in pain. Mice bred to have fewer of these particular receptors did not scratch themselves when given an opioid, but they did exhibit the telltale mouse signs of pain relief, such as less flinching when researchers flicked their tails.
Now that scientists know that pain relief and itching can be decoupled, they will try to make itch-free opioid drugs a reality. Already a subscriber? Sign in. Thanks for reading Scientific American. Create your free account or Sign in to continue. See Subscription Options. This medicine may make you dizzy, drowsy, or lightheaded. Do not drive or do anything else that could be dangerous until you know how this medicine affects you. Using narcotics for a long time can cause severe constipation.
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Error Email field is required. Error Include a valid email address. And this is what presents itself as itching. 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.
Currently there are about orphan receptors in humans. They are "orphan" because, though we know they exist, we don't yet know what they do. The Roth lab screens these receptors against thousands of small molecules to find out what might activate them. This process involves a combination of physical screening and computational modeling.
Once that tentative picture was in place, we were able to use computational tools to create a more precise model of the site. The computer modeling, performed by co-first author Joel Karpiak, a graduate student at the University California at San Francisco, tested 3. The physical data combined with the computational models allowed the researchers to create a chemical probe designed to interact specifically with MRGRPX2.
This new tool made it possible to gain a more precise understanding of this receptor's effects without the noise of other receptors. An opioid might activate the orphan receptor, but it might also activate other receptors that it interacts with. Imagine trying to recreate a musical score by listening to an orchestra perform a piece of music.
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