Emerging Insights On The Itch Sensation

“I’ve got an itch to tell you something,” Dr. Hans Zarkov said to me. Hans Zarkov has been sequestered in a lab outside Basel, Switzerland on the Rhine River ever since Queen eternally memorialized him in their famous song “Flash.” As everyone knows, Zarkov is the fictional scientist from NASA in the Flash Gordon comic series. However, what many don’t know is that he really is one of the world’s experts in the study of the sensation of itch.

Zarkov started explaining to me what they have recently discovered about the sensation of itch. “First, itch has to be remembered as a protective sensation and it is what reminded the caveman not to let the stinging nettles come in contact with the twig and berries.”

I had to start laughing as I never would have thought of that aspect of the sensation, only the fact that we relate an itch to stinging bug bites and other noxious stimuli. Yet his allusion did make me squirm a little. “Well, they say if you’ve got an itch, just scratch it. Then give them some diphenhydramine, a topical steroid and, in severe cases, a prednisolone dosepak,” I responded after suppressing my laughter. 

“For all these years, we have thought that histamine was the sole culprit in the transmission of the sensation of itch and now we know that there is another mediator than the histamine receptor. In fact, it now appears that there is a separate set of neurons dedicated solely to itch,” Zarkov boasted.

“So what you are saying is that the sensations of itch and pain are not as closely associated as once thought, and itch is in fact conducted to the central nervous system (CNS) via special itch neurons?” I questioned.

“Yes, you’ve got it,” he told me. “We took mice and knocked out different receptors, and then applied things like capsaicin to them. Voilà! No itch in the mice without the newly discovered receptor MrgprA3 (Mas-related, G-protein coupled receptors).”

I spent the rest of the day with Zarkov in his itch chamber and learned the following points.

1. There is an interesting relationship, intimate in fact, between pain and itch. An example of this is when a healing surgical wound gets to the point of decreasing pain, itch will sometimes take over. How often have you seen patients who tell you that?
2. While scratching can be a somewhat pleasant central nervous system stimulant, when we do it in the presence of itch, it can be highly rewarding and mitigate the sensation to a tolerable situation for the patient. In fact, in magnetic resonance imaging (MRI) studies, scratching lights up the brain’s reward system, similarly to what occurs with drug abuse.¹
3. In chronic cases of itch, scratching over time can be amplified, creating more addiction to scratching over time. It is no longer valid to tell patients not to scratch. They simply cannot help it. They are addicted. The better advice is to tell them the scratch carefully.
4. If diphenhydramine does not work, it is because you are only hitting one receptor and not the true itch receptor, which histamine helps mediate to a lesser extent. 
5. We basically have only three ways to treat itch right now: attacking the histamine receptor; steroids (topical or parenteral); and finding the source of the pruritus and getting rid of it via allergy testing.
6. Scratching can actually be contagious from one individual to another. See somebody scratch and if you have the littlest of itch, you will find yourself doing it as well. It seems we have been hardwired for that from our early Paleolithic ancestors.
7. In the future, there will be new classes of drugs to treat the Mrgpr3A receptor that will likely improve pain management and decrease opioid demand.
8. There are spinal neurons and signaling molecular compounds solely related to the transmission of the sensation of itch.

Now these are some very cool facts and insights into what makes us scratch, and the phenomenon of itching. So at least the next time a patient tells you that his or her incision has started to itch, you will remember the complex association of itch and pain. 

If you now have the itch for a great review on the complexity of the science of itch and what was the genesis of this DPM Blog, go to the May 2016 issue of Scientific American. You can find the article, “The Maddening Sensation of Itch,” on page 39. As for Dr. Hans Zarkov, I left his lab as he had his arms stretched wide, singing at the top of his lungs, “Flash, savior of the Universe …”

Reference

1. Papoiu AD, Nattkemper LA, Sanders KM, et al. Brain’s reward circuits mediate itch relief: a functional MRI study of active scratching. PLoS One. 2013; 8(12):e82389.