Sensory neuron-specific deletion of TRPA1 results in mechanical cutaneous sensory deficits

KJ Zappia, CL O'Hara, F Moehring, KY Kwan… - Eneuro, 2017 - eneuro.org
KJ Zappia, CL O'Hara, F Moehring, KY Kwan, CL Stucky
Eneuro, 2017eneuro.org
The nonselective cation channel transient receptor potential ankyrin 1 (TRPA1) is known to
be a key contributor to both somatosensation and pain. Recent studies have implicated
TRPA1 in additional physiologic functions and have also suggested that TRPA1 is
expressed in nonneuronal tissues. Thus, it has become necessary to resolve the importance
of TRPA1 expressed in primary sensory neurons, particularly since previous research has
largely used global knock-out animals and chemical TRPA1 antagonists. We therefore …
Abstract
The nonselective cation channel transient receptor potential ankyrin 1 (TRPA1) is known to be a key contributor to both somatosensation and pain. Recent studies have implicated TRPA1 in additional physiologic functions and have also suggested that TRPA1 is expressed in nonneuronal tissues. Thus, it has become necessary to resolve the importance of TRPA1 expressed in primary sensory neurons, particularly since previous research has largely used global knock-out animals and chemical TRPA1 antagonists. We therefore sought to isolate the physiological relevance of TRPA1 specifically within sensory neurons. To accomplish this, we used Advillin-Cre mice, in which the promoter for Advillin is used to drive expression of Cre recombinase specifically within sensory neurons. These Advillin-Cre mice were crossed with Trpa1fl/fl mice to generate sensory neuron-specific Trpa1 knock-out mice. Here, we show that tissue-specific deletion of TRPA1 from sensory neurons produced strong deficits in behavioral sensitivity to mechanical stimulation, while sensitivity to cold and heat stimuli remained intact. The mechanical sensory deficit was incomplete compared to the mechanosensory impairment of TRPA1 global knock-out mice, in line with the incomplete (∼80%) elimination of TRPA1 from sensory neurons in the tissue-specific Advillin-Cre knock-out mice. Equivalent findings were observed in tissue-specific knock-out animals originating from two independently-generated Advillin-Cre lines. As such, our results show that sensory neuron TRPA1 is required for mechanical, but not cold, responsiveness in noninjured skin.
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