The science of itch: Learning to quiet an overcharged nervous system


Gil Yosipovitch, MD

Itch is a condition often associated with diseases from psoriasis and atopic dermatitis to kidney disease, liver disease, and lymphoma, but it has become clear that it is more than that — it also is its own disease state. Research has found that even though it has links to other diseases, itch is the result of interactions between nerves connecting the skin to the brain.

“An important concept in my work is that the skin is hypersensitized,” Gil Yosipovitch, MD, said in an interview before his Sunday lecture “Itch.” “Imagine the nervous system is hard-wired, like your house. It is as if someone has come to the house and rewired everything in the walls, but has hidden the ‘off’ switch.

“The idea is that the nerves are firing too much, which is why when patients have even a non-itch stimuli, such as clothing or temperature changes, they feel itch.”

Dr. Yosipovitch, professor and chair of the department of dermatology and director of the Temple Itch Center at the Lewis Katz School of Medicine, Temple University, discussed his years of research when he delivered the Marion B. Sulzberger, MD, Memorial Award and Lectureship.

A foundation of Dr. Yosipovitch’s research is that there are two major neuronal pathways — histaminergic and non-histaminergic. For chronic itch, the non-histaminergic is more important. Itch carries the interactions among keratinocytes, nerves in the epidermis and dermal epidermal junction, and immune cells. These interactions are the result of an overcharged nervous system that sends the information to the nerve fibers in the spinal cord.

“How do I treat chronic itch? I rarely use antihistamines,” he said. “For decades, this is what we were using, but these drugs usually cause patients to be drowsy. They may forget about their itch, but the drugs do not address the itch in the majority of the cases.

“The current treatments that I use in my armamentarium are to quiet the nerve activity by drugs we use in the periphery — local anesthetics, ion channel blockers, amitryptiline, and lidocaine, and topicals such as pramoxine, menthol, and ketamine.”

Those drugs put the nerves to sleep, but a better, long-term approach may be to retrain the nerves to respond normally, Dr. Yosipovitch said. Neuromodulating drugs, such as gabapentin and pregabalin, anti-depressant drugs, and kappa opioids such as butorphanol may be used in this effort.

“There is no quick fix for all types of itch,” he said. “It is very complex and requires the use of a comprehensive approach, including topical, oral, or systemic non-pharmacological approaches.

“I have a message of hope because we have so many new targets that have been found recently, and there are several drugs in the pipeline that target itch pathways in the skin, spinal cord, and brain.”

Dr. Yosipovitch also is a supporter of looking beyond drugs to help patients cope with debilitating chronic itch.

“I take a holistic approach, meaning that along with this support of treatments pharmacologically, we also use an intensive program of multidisciplinary techniques to address coping,” he said. “We have initiated techniques based on other models from Europe and Asia that are helpful to reduce the patient’s misery.”

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