Sensory Neuron-Specific Deletion of TRPA1 Results in Mechanical Cutaneous Sensory Deficits. eNeuro 2017;4(1)
Date
03/18/2017Pubmed ID
28303259Pubmed Central ID
PMC5346175DOI
10.1523/ENEURO.0069-16.2017Scopus ID
2-s2.0-85031943687 (requires institutional sign-in at Scopus site) 44 CitationsAbstract
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.
Author List
Zappia KJ, O'Hara CL, Moehring F, Kwan KY, Stucky CLAuthor
Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCalcium
Cells, Cultured
Cold Temperature
Female
Ganglia, Spinal
Hot Temperature
Lumbar Vertebrae
Male
Mechanotransduction, Cellular
Mice, Knockout
Microfilament Proteins
Nociception
Promoter Regions, Genetic
RNA, Messenger
Sensory Receptor Cells
Sensory Thresholds
Skin
TRPA1 Cation Channel
Touch
Transient Receptor Potential Channels
