The role of the ion channel, TRPA1, in itch transduction in the mammalian peripheral nervous system.
- Author(s): Wilson, Sarah Ruth
- Advisor(s): Bautista, Diana M
- et al.
Itch is defined as an unpleasant sensation that evokes a desire to scratch. In contrast to acute itch that is transient, chronic itch is a persistent, debilitating condition for which there are few treatment options. Chronic itch accompanies a number of skin diseases and systemic conditions, as well as a variety of neurological disorders. However, little is known about the molecules and cell types that mediate acute or chronic itch in primary sensory neurons and skin.
We have established an essential role for the ion channel, TRPA1, in multiple forms of both acute and chronic itch. We have shown that TRPA1 is required for neuronal activation and itch behaviors in mice downstream of acute exogenous and endogenous itch compounds. Similarly, TRPA1 is required for itch behavior and itch-evoked expressional changes in both sensory neurons and skin in a mouse model of dry skin.
We have also identified a novel itch-causing compound: Thymic Stromal Lymphopoietin (TSLP). Numerous studies suggest that the epithelially-derived cytokine TSLP acts as a master switch that triggers both the initiation and maintenance of the chronic itch disease atopic dermatitis. Our work demonstrates that TSLP activates sensory neurons directly and leads to acute itch behaviors. TRPA1 is required for both TSLP-evoked neuronal activation and itch behaviors. Taken together, our work shows that TRPA1 is a master regulator of itch signaling.