Scientists Identify a Culprit for Chronic Itch

At a Glance:

• An immune substance called oncostatin M was found to sensitize and enhance the activity of itch-sensing neurons.
• A drug that blocks oncostatin M activity reduced scratching in a mouse model of chronic itch, suggesting a treatment strategy for persistent itchy skin conditions.

Chronic itch is a common yet hard-to-treat symptom of many inflammatory skin conditions, such as psoriasis. The urge to constantly scratch can seriously impair a person’s quality of life and lead to permanent skin damage. To find an effective treatment, scientists need to better understand how chronic itch develops.

Short-lived itch—from an insect bite, for example—arises when immune substances released by the body activate itch-sensing nerve fibers in the skin. The signal is relayed to the brain, where it is perceived as the sensation of itch. But scientists haven’t understood how this process may become chronic.

A research team led by NIDCR’s Mark Hoon, PhD, examined skin from people and mice with skin diseases associated with chronic itch. Results were published in Science Translational Medicine.

The team found that skin samples from people with chronic itch-related conditions made high levels of an immune signaling molecule called oncostatin M (OSM). OSM sends immune signals to cells by stimulating protein receptors on their surfaces. Although OSM had previously been linked to inflammatory diseases such as arthritis, there had been little evidence of its involvement in itch.

The scientists showed that itch-sensing neurons in both mice and humans produce the receptor for OSM. This suggests that OSM can affect the activity of these cells.

To find out if this was the case, the researchers exposed itch-sensing mouse neurons grown in a dish to OSM. They tested neuron responses by measuring changes in their electrical activity. Unlike most itch-inducing substances, OSM did not directly activate the itch neurons. Instead, it enhanced the neurons’ responses to histamine, an itch-inducing molecule released by the body during immune reactions. Prolonged exposure to OSM also increased the baseline excitability of the neurons—meaning they became sensitive to even small stimuli.

In a similar fashion, injection of OSM into the skin of mice heightened their histamine-induced scratching. Histamine given alone triggered immediate but short-lasting scratching. In contrast, when OSM was injected on its own, mice slowly developed scratching behavior after a delay of about 30 minutes.

OSM’s effects on scratching were partially reversed by removing the OSM receptor. In a mouse model of psoriasis-induced chronic itch, scratching was almost entirely eliminated by treatment with a drug that blocks the OSM receptor.

“Our findings suggest that prolonged elevation of OSM in the presence of other itch-inducing agents can switch short-term itch responses into longer-lasting episodes,” Hoon explains. “Small molecule drugs that block OSM’s activity could be promising therapies for chronic itch.”

—by Catherine Evans, PhD

Adapted from an article in NIH Research Matters, November 30, 2021.

Reference

Oncostatin M can sensitize sensory neurons in inflammatory pruritus. Tseng PY, Hoon MA. Sci Transl Med. 2021 Nov 10;13(619):eabe3037.

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