A Sensory-Labeled Line for Cold: TRPM8-Expressing Sensory Neurons Define the Cellular Basis for Cold, Cold Pain, and Cooling-Mediated Analgesia
Open Access
- 13 February 2013
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 33 (7), 2837-2848
- https://doi.org/10.1523/jneurosci.1943-12.2013
Abstract
Many primary sensory neurons are polymodal, responding to multiple stimulus modalities (chemical, thermal, or mechanical), yet each modality is recognized differently. Although polymodality implies that stimulus encoding occurs in higher centers, such as the spinal cord or brain, recent sensory neuron ablation studies find that behavioral responses to different modalities require distinct subpopulations, suggesting the existence of modality-specific labeled lines at the level of the sensory afferent. Here we provide evidence that neurons expressing TRPM8, a cold- and menthol-gated channel required for normal cold responses in mammals, represents a labeled line solely for cold sensation. We examined the behavioral significance of conditionally ablating TRPM8-expressing neurons in adult mice, finding that, like animals lacking TRPM8 channels (Trpm8−/−), animals depleted of TRPM8 neurons (“ablated”) are insensitive to cool to painfully cold temperatures. Ablated animals showed little aversion to noxious cold and did not distinguish between cold and a preferred warm temperature, a phenotype more profound than that ofTrpm8−/−mice which exhibit only partial cold-avoidance and -preference behaviors. In addition to acute responses, cold pain associated with inflammation and nerve injury was significantly attenuated in ablated andTrpm8−/−mice. Moreover, cooling-induced analgesia after nerve injury was abolished in both genotypes. Last, heat, mechanical, and proprioceptive behaviors were normal in ablated mice, demonstrating that TRPM8 neurons are dispensable for other somatosensory modalities. Together, these data show that, although some limited cold sensitivity remains inTrpm8−/−mice, TRPM8 neurons are required for the breadth of behavioral responses evoked by cold temperatures.Keywords
This publication has 62 references indexed in Scilit:
- Population coding of somatic sensationsNeuroscience Bulletin, 2012
- Oxaliplatin‐induced cold hypersensitivity is due to remodelling of ion channel expression in nociceptorsEMBO Molecular Medicine, 2011
- TRPV1-lineage neurons are required for thermal sensationThe EMBO Journal, 2010
- VGLUT2-Dependent Glutamate Release from Nociceptors Is Required to Sense Pain and Suppress ItchNeuron, 2010
- The development of peripheral cold neural circuits based on TRPM8 expressionNeuroscience, 2010
- TRPM8, but not TRPA1, is required for neural and behavioral responses to acute noxious cold temperatures and cold-mimetics in vivoPain, 2010
- Ablation of TrpV1 neurons reveals their selective role in thermal pain sensationMolecular and Cellular Neuroscience, 2010
- Cellular and Molecular Mechanisms of PainCell, 2009
- The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perceptionThe EMBO Journal, 2009
- Topographically Distinct Epidermal Nociceptive Circuits Revealed by Axonal Tracers Targeted to MrgprdNeuron, 2005