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Open Access Highly Accessed Research

Sensory discrimination between innocuous and noxious cold by TRPM8-expressing DRG neurons of rats

Ignacio Sarria1, Jennifer Ling1, Guang-Yin Xu2 and Jianguo G Gu1*

Author Affiliations

1 Department of Anesthesiology and the Graduate Program in Neuroscience, The University of Cincinnati College of Medicine, PO Box 670531, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA

2 Institute of Neuroscience, Department of Neurobiology, Key Laboratory of Pain Basic Research and Clinic Therapy, Soochow University, Suzhou, 215123, PR China

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Molecular Pain 2012, 8:79  doi:10.1186/1744-8069-8-79

Published: 24 October 2012

Abstract

The TRPM8 channel is a principal cold transducer that is expressed on some primary afferents of the somatic and cranial sensory systems. However, it is uncertain whether TRPM8-expressing afferent neurons have the ability to convey innocuous and noxious cold stimuli with sensory discrimination between the two sub-modalities. Using rat dorsal root ganglion (DRG) neurons and the patch-clamp recording technique, we characterized membrane and action potential properties of TRPM8-expressing DRG neurons at 24°C and 10°C. TRPM8-expressing neurons could be classified into TTX-sensitive (TTXs/TRPM8) and TTX-resistant (TTXr/TRPM8) subtypes based on the sensitivity to tetrodotoxin (TTX) block of their action potentials. These two subtypes of cold-sensing cells displayed different membrane and action potential properties. Voltage-activated inward Na+ currents were highly susceptible to cooling temperature and abolished by ~95% at 10°C in TTXs/TRPM8 DRG neurons, but remained substantially large at 10°C in TTXr/TRPM8 cells. In both TTXs/TRPM8 and TTXr/TRPM8 cells, voltage-activated outward K+ currents were substantially inhibited at 10°C, and the cooling-sensitive outward currents resembled A-type K+ currents. TTXs/TRPM8 neurons and TTXr/TRPM8 neurons were shown to fire action potentials at innocuous and noxious cold temperatures respectively, demonstrating sensory discrimination between innocuous and noxious cold by the two subpopulations of cold-sensing DRG neurons. The effects of cooling temperatures on voltage-gated Na+ channels and A-type K+ currents are likely to be contributing factors to sensory discrimination of cold by TTXs/TRPM8 and TTXr/TRPM8 afferent neurons.