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Oct 16, 2013

Chronic Itch Linked to Pathway Glitch

  • Chronic itching, or pruritis, appears to involve more than the usual itch signals. Instead, it seems that chronic itching results when pain signals become involved, intensifying the itch sensation. Exactly how pain signaling pathways join in transmitting itch signals was not at all clear—until it caught the attention of scientists led by Zhou-Feng Chen, Ph.D., the director of Center for the Study of Itch at Washington University.

    These scientists have implicated a protein called BRAF, which had already been known to play a role in the body’s pain response. After experimenting with mice in which BRAF was always active, the scientists found that BRAF also continually sent signals inside itch neurons.

    The mice, which had been expected to be prone to feeling pain rather than itching, scratched spontaneously. To the scientists’ surprise, they had developed a mouse model of chronic itch.

    “In normal itching, there’s a fixed pathway that transmits the itch signal,” said Dr. Chen. “But with chronic itching, many neurons can be turned into itch neurons, including those that typically transmit pain signals. That helps explain why chronic itching can be so excruciating.”

    The scientists published their results online October 15 in the Journal of Clinical Investigation (“Chronic itch development in sensory neurons requires BRAF signaling pathways”). In their paper, the scientists said, “We identify the BRAF pathway as an upstream regulator of expression of a cohort of itch mediators in mouse sensory neurons. Our data further demonstrate that GRP/GRPR signaling plays an important role in the initiation and maintenance of long-lasting itch in three distinct genetic and/or clinically relevant chronic itch models.”

    GRP, or gastrin-releasing peptide, is a substance that carries itch signals to a gene called GRPR, or gastrin-releasing peptide receptor, in the spinal cord. In the new study, GRP and GRPR activity was doubled in the genetically altered mice, which could account for some of the increase in the intensity of itching.

    In addition, other genes normally activated by pain were also turned on in the itch pathway, further intensifying the itch sensation. Or, as the scientists stated, “A phenotypic switch from nociceptors to pruriceptors underlies the transition from acute itch signaling to pathological itch state.”

    The findings suggest that targeting proteins in the BRAF pathway may open new avenues for treating chronic itch, a condition in which few therapies are effective. One possibility includes using drugs that are prescribed to treat pain.

    “In people, chronic itching can last for weeks, months, or even years,” Dr. Chen said. “These mice are helping us to understand the pathways that can be involved in transmitting itch signals and the many contributors to chronic itching. There are many pathways leading from BRAF, and all of these could be potential targets for anti-itch therapies.”



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