Key to chronic eczema itch may lie in special ion channel

Recently scientists reported the discovery of an “itch molecule” (Nppb)  responsible for conveying the itch signal across the synapse from sensory neurons in the skin to neurons in the dorsal horn of the spinal cord.

The media made a great deal of this study, which laid out a substantial model for how we feel itch.

Something I hadn’t noticed, though, was that the Science study considered only a subset of neurons involved in sensing itch—those that are activated by histamine. These neurons, at the itch-sensing end, have a type of ion channel called “TRPV1” that detects histamine and other substances, or “pruritogens,” that induce itch.

An ion channel is a kind of gate that opens when a key--such as a histamine molecule--binds to it. The open gate lets in sodium or potassium ions. When this happens to ion channels in a neuron, the neuron sends an electrical pulse down its length, transmitting information, such as a sensation of itch.

But there are other triggers for itch besides histamine. “Histamine-independent” itch is particularly important in the chronic itch experienced by eczema patients. (And that's why antihistamines don't do us any good.)

Histamine-independent itch is transmitted by neurons that possess TRPA1 ion channels. A new study, published in the Journal of Neuroscience, shows that mice only feel chronic itch if they have neurons expressing TRPA1 channels. Strikingly, the scientists show that knocking out TRPV1 channels (the histamine-dependent kind) does not affect the ability of mice to feel chronic itch.

As a model of chronic itch, the researchers shaved the cheeks of lab mice and exposed the skin to drying chemicals over a period of a few days. The mice scratched their cheeks and developed classic signs of dry, itchy skin--unless their TRPA1 channels had either been genetically deleted or inhibited by a drug,in which cases they hardly scratched at all.

The researchers were also interested in whether the itch-scratch cycle affected the sensation of itch. If you don’t scratch an itch, does it get better or worse? The answer appears to be that if you (or, by proxy, a lab mouse) have an itch on your back that you can only scratch by rubbing it against the wall, it may torment you, but when measured by objective standards, skin that you don’t scratch ends up in better shape.

We can draw two practical conclusions from this work, which was led by Diana Bautista at UC Berkeley: that blocking TRPA1 channels with a drug in cream or ointment form could be a potential solution to the chronic itch of eczema; and that it really does appear that if you can break the itch-scratch cycle, your skin will be better off.

Now, we all know how difficult it is to stop scratching. It’s not as easy as saying that you’ll stop. But this type of research certainly highlights the positive feedback of habit-reversal, which uses psychiatric techniques to reduce habitual scratching. Scratch less…and you’ll feel less itchy.

I do have one question: does the molecule Nppb, reported in the Science paper two weeks ago, transmit chronic itch signals as well as histamine-induced itch? If so, it is still a valuable target for further research into eczema therapies.