TRPA1 channels are signal amplifiers of itch responses

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NIDCR	SENSYS-1

* FARE Award Winner

Authors

• P Orestes
• SK Mishra
• SM Tisel
• MA Hoon

Abstract

Itch is an important, though often overlooked, aspect of many skin, systemic and nervous system disorders. Indeed, antihistamine-resistant itch is the most commonly cited reason for non-compliance with the anti-malarial drug, chloroquine. Current therapies for treating itch are often ineffective, leading our search to better understand the mechanisms behind the coding of itch in sensory neurons. The non-specific cation channel, TRPA1, has been known for its role as the mustard oil receptor, but recent studies have also demonstrated its role in itch. Indeed, TRPA1-deficient mice exhibit significantly decreased responses to pruritogens (itch-inducing agents) such as chloroquine. Here, we use a transgenic mouse model that overexpresses TRPA1 (TrpA1-V1) to further examine its role in itch pathways. TrpA1 overexpressing mice have 50% more neurons that respond to capsaicin, histamine, and mustard oil compared to wild type littermates in calcium imaging experiments. These mice also display increased scratching behavior after intradermal choloroquine, SLIGRL-NH2 (both non-histamine dependent) and histamine injections. Though TRPA1 -/- mice still respond to some pruritogens, our TrpA1-V1 animals demonstrate a gain of function— cells can be recruited and signal strength increased with altered ion channel expression, highlighting TRPA1’s role as a signal amplifier in sensory neurons.

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