To Scratch an Itch

It’s officially mid-July, and in the ever-humid concrete jungle that is New York City, mosquitoes swarm the streets looking for some nice, hot blood. Last week I had a blast barbecuing at a friend’s house until the mosquitoes arrived. I was immediately overcome by an itchiness so intense, I would have traveled miles for bug spray; luckily, my friend had some, but the damage was done. I counted over twenty bites the next day. Imagine the itching. It was pure misery. Now imagine that itching, all over, all the time.


Believe it or not, there is more than one kind of itch. Acute itching, like the type caused by my pesky bug bites is quite unpleasant and only seems to be cute relative to the alternative: chronic itching. Much like chronic pain, it is constant, unbearable and difficult to treat because doctors don’t know enough about how itching is processed in the brain.  To further complicate things, chronic itching is categorized into sub-itches based on their causes.

Scientists know about the different itches, but have been arguing over whether or not they activate the same or different pathways in the brain for a while. In a study in July’s issue of Nature Neuroscience, however, Roberson et al. helps to clear things up. By looking at different itching in mice, it was revealed that there are sensory neurons specially designed for generating itch and that different types of itch are processed through distinct pathways.

Know your itches.

An itch starts with a pruritogen, an exogenous or endogenous compound that binds to specific receptors on specific neurons that activate and send a signal to the brain: “hey, it’s, like, super itchy over here.” The main types of pruritogens are histamine-dependent (hives) and histamine-independent (eczema, allergic itch and dry skin). Histamine-dependent itches are treated pretty well with antihistamines such as Benadryl, but that’s not always the case with histamine-independent itches.

In this study, scientists used nerve blocks in neurons that specifically react to histamine or non histamine (chloroquine, an antimalarial medication that causes itchiness). They used QX-314, a derivative of a common local anesthetic called lidocaine to turn off the cells.


When histamine or chloroquine binds to its corresponding receptor on an itch-sensitive neuron, it activates ion channels (TRPV1 or TRPA1, respectively). These channels open big pores that allow QX-314, normally too big to permeate the cell membrane, to flow into the cell. Once inside, QX-314 changes the electric charge of the cell and shuts it down. Thus, if the drug is successful at blocking cellular activity, or stopping the itch, the scientist knows that neuron is specific to that pruritogen because otherwise the drug couldn’t have gotten in.

By mixing and matching neurons, receptors, pruritogens and QX-314 and looking at itchy mice, scientists were able to determine that indeed, there are separate pathways for histamine and histamine-independent itches. For us humans, this knowledge won’t kill mosquitoes or acute itching. What it can do is bring us closer to understanding how chronic itching is processed in the brain. It opens the door for new, specific therapies that could target only pathologically activated itch-sensitive neurons, while sparing functionality of the others. – by JoAnna Klein

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