For several years it’s been known that itch and pain signals from the skin are carried by different types of neuron to the spinal cord and brain. But there’s more than one kind of itch. Scientists have now clearly identified at least two types of itch neuron—one that responds to histamine and a second type that responds to other itch-provoking molecules.
These results could lead to drugs that selectively shut down chronic itch in eczema patients but leave the rest of the sensory system intact.
Some itch is caused by histamine, which triggers an itch signal in certain neurons. But histamine is not the main source of itch for eczema patients. In eczema, most itch has its origins in allergy, when mast cells release “pruritogens” that bind to receptors on itch neurons.
For a long time it was an open question whether histamine and the other pruritogens were triggering itch signals in the same neurons, or different types that scientists could distinguish experimentally.
In late May, researchers led by Alexander Binshtok at the Hebrew University in Jerusalem and Clifford Woolf at Harvard Medical School reported results that clearly showed histamine and non-histamine itch signals are carried by different neurons. The research was published in the journal Nature Neuroscience.
The scientists used a novel two-stage experimental technique to shut the two neuron types down independently. Perhaps someday a similar technique might be embodied in an anti-itch therapy.
What they did was to exploit the fact that when neurons detect histamine and pruritogens, large-diameter channels open in the neurons to let in ions (charged particles) that initiate the electrochemical itch signal, which relies on sodium and potassium.
First, the scientists treated mice with either histamine or a non-histamine pruritogen. At the same time they injected the mice with QX-314, a molecule that blocks sodium ion channels (which are very small-diameter). The large-bore ion channels opened to let in sodium, potassium, and QX-314.
Thereafter, those neurons were unable to fire itch signals, because their sodium channels were blocked by QX-314. The scientists showed that when they dosed the mice with histamine and QX-314, one group of neurons didn’t work (and the mice didn’t scratch). When they dosed the mice with other pruritogens and QX-314, the histamine itch neurons worked, but other subsets of neurons were shut off (and the mice didn’t scratch).
The scientists’ technique is not directly translatable to therapy, because this study was conducted in mice and involved injection, which is not practical for daily use. But the molecular action they were studying takes place in the upper skin layers, and one could imagine that someday a cream or ointment might be developed that would include two components: one to open large-bore ion channels that detect pruritogens, and another to block the electrochemical signals in those neurons.
Hat tip to Ryan.
PS in a recent post I discussed the difference between TRPV1 ion channels, required for histamine itch, and TRPA1 channels, required for chronic itch. These are the “large-bore” channels mentioned above. Trivia: To trigger a histamine itch signal in a neuron, histamine must activate both TRPV1 and the H1 histamine receptor. To trigger a non-histamine itch signal in a neuron, a pruritogen must activate both TRPA1 and a special pruritogen receptor–“MrgprC11” in the case of dry skin.
End Eczema
