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IISc Identifies Stress-Activated Hypothalamic Switch That Suppresses Itch

In mice, the pathway funnels to the periaqueductal gray, with psoriasis-like inflammation derailing the suppression.

Overview

  • IISc researchers report in Cell Reports that a defined lateral hypothalamic neuron population activated by acute stress directly modulates itch in genetically engineered mice.
  • Artificial activation of these neurons reduced scratching in both chloroquine-induced and psoriasis-like models, while silencing them abolished stress-driven itch relief, establishing necessity and sufficiency.
  • Anterograde tracing mapped projections to key brainstem nodes involved in itch control, with targeted experiments identifying the periaqueductal gray as the predominant mediator.
  • The same stress-sensitive neurons became hyper-excitable in psoriasis-like chronic inflammation and failed to suppress itch, providing a neural basis for stress-related worsening of persistent pruritus.
  • The work remains preclinical in mice, activation also produced anxiety-like behavior, and the team plans molecular characterization and tests of additional stress modalities to inform future therapies.