We all feel the urge to scratch from time to time. But what if it becomes a persistent and chronic problem?
Itch, also known as ‘pruritus’, is an unpleasant sensation in the skin that evokes the desire or reflex of scratching behaviour. Like pain, itch serves as a self-protective or warning system under normal conditions, but not all itches go away with a simple scratch. Roughly 15 percent of itch patients suffer relentless, long-term itch to the extent that it can greatly reduce their quality of life.
Chronic itch is often caused by conditions such as atopic dermatitis (eczema), contact dermatitis or allergic contact dermatitis, by liver or kidney disease, by metabolic disorders such as diabetes or by medications: terminally ill cancer patients, for example, often experience such severe whole-body itch in response to morphine that many choose to live in pain rather than take the medication.
In Prof Martin Steinhoff’s laboratory, we are discovering more about the mechanisms of itch with a view to short-circuiting those mechanisms in patients who suffer from chronic itch. Anti-histamine drugs can quell itch in some cases, but for many people anti-histamines do not solve the problem, so we are looking at other approaches.
A large part of our work focuses on a protein called endothelin-1, which was previously known to mediate itch in animal studies, but was little understood in humans.
Endothelin-1 needs to react with a different molecule called the endothelin-A receptor (ETAR) in order to cause the itching sensation. Our lab has shown that a specific enzyme, called endothelin-converting enzyme 1 (ECE-1), regulates this reaction. This enzyme stops endothelin-1 reacting with the endothelin-A receptor and so stops the feeling of itch.
Targeting this pathway could represent a new form of intervention for people who do not respond to anti-histamine drugs as a therapy for itching. We have already shown in an animal model that we could turn the dial up or down on the level of itch by targeting molecules involved in this endothelin pathway.
We have also identified that a molecule called interleukin-31, or IL-31, is increased in the skin of animal models and humans with eczema and prurigo (itchy lesions on the skin) and we identified the cells of the immune system that are making this molecular signal.
Again, this is a potential target for therapies where the itching signal is affecting quality of life and is not responding to existing treatments.