A new approach for investigating the mechanism underlying chronic itch associated with atopic dermatitis

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15203
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pain science
• Research Institution: Kyushu University
• Principal Investigator: Tsuda Makoto 九州大学, 薬学研究院, 教授 (40373394)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 慢性掻痒 / アトピー性皮膚炎 / 脊髄後角 / アストロサイト / STAT3

Outline of Final Research Achievements

The mechanisms by which itch turns into a pathological chronic state are poorly understood. This study revealed that in a model of atopic dermatitis, reactive astrocytes were persistently observed in the spinal dorsal horn (SDH) segments that corresponded to lesioned, itchy skin. A pharmacological blockade or a genetic conditional knockout of STAT3 suppressed the reactive state of SDH astrocytes and chronic itch. Furthermore, atopic dermatitis mice exhibited sensitization of itch signaling in the SDH, and, interestingly, the sensitization was normalized by suppressing reactive astrocytes. Moreover, we identified lipocalin-2 (LCN2) as an astrocytic STAT3-dependent upregulated factor that was crucial for chronic itch. These findings indicate a pivotal role of STAT3-dependent reactive astrocytes in chronic itch.

Free Research Field

神経薬理学