Researchers Target Signaling Pathways to Develop Pruritus Treatments

An update of that research with a look at where it may be headed was presented March 24 at the AAD Annual Meeting during “Chronic Pruritus: Bedside to Bench Perspectives” (S042). The session featured researchers focusing on basic science followed by clinicians focusing on treatment in four areas: the basics of itch, itching related to atopic dermatitis and eczema, neuropathic itch, and itch in the elderly.

“The scientific community in dermatology and neurosciences has been elucidating the itch pathways and signaling systems. This is an immunologic and neurologic process,” said Timothy G. Berger, MD, co-director of the course. “Something happens to the skin that gets communicated to a nerve, and that is perceived as itching. That pathway from the event in the skin to the perception of itch is being tracked. What nerves carry the signal and where they are received in the brain — all of that is being worked out.

“Science is moving forward in this area. There may not be specific targets yet, like in psoriasis, but we envision there being specific blockers of the signaling molecules or signaling nerves that mediate itch.”

This research has greatly altered the work to develop treatments for pruritus, which is the most common complaint of dermatology patients.

“Even the preliminary knowledge we have of the basic mechanisms of pruritus suggests that we think about treating it in a completely different way,” said Dr. Berger, clinical professor of dermatology at the University of California, San Francisco. “While we do not have specific drugs, like TNF inhibitors for psoriasis, we do have new paradigm-changing concepts of treatment that have changed the way a lot of us who have managed itch approach the problem.”

Progress is being made in treating chronic itch that is linked to a hypersensitization phenomenon of nerve fibers by targeting the nerves, said Gil Yosipovitch, MD, the course director.

“There are drugs that work on this pathway of sensitization of nerve fibers. A good example is gabapentin and pregabalin, which are drugs that do work for chronic pain and chronic itch. A combination of them with some antidepressant drugs enables us to reduce that sensitization,” said Dr. Yosipovitch, professor and chair, department of dermatology and director of the Temple Itch Center, Temple University School of Medicine, Philadelphia.

Still other drugs target receptors, but finding the right combination is key.

“There is an imbalance in chronic itch between activation of mu receptors and kappa receptors. There are drugs that work on reducing mu, which is the morphine receptor. We know it inhibits pain, but it increases itch. Now, we have drugs that mitigate this effect, such as kappa receptor agonists. This field is evolving into treatments,” Dr. Yosipovitch said.

Still another option is the use of immunosuppressants for inflammatory skin diseases with chronic itch, such as atopic eczema and psoriasis, but it is not clear how they work, he said.

The final area discussed was itch among the elderly, which is a growing complaint related to the physiologic changes of aging.

“The field has grown significantly and the science behind it has been revolutionized in the last decade,” Dr. Yosipovitch said. “We know a lot more, but the science has to be translated into understanding treatments, identifying the problems where the core issues are, and finding ways to address them.”