Journal
NATURE NEUROSCIENCE
Volume 13, Issue 7, Pages 861-U106Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2581
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Funding
- Medical Research Council
- National Institute on Drug Abuse
- National Institute of Neurological Disorders and Stroke
- Ministry of Education, Science and Technology of Korea [M103KV010015-06K2201-01510]
- National Research Foundation of Korea [KRF-2008-331-E00457, 2009-0076543]
- US-Israel Binational Science Foundation [2005036]
- National Research Foundation of Korea [2009-0076543, 2008-331-E00457] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Medical Research Council [MC_U105185857] Funding Source: researchfish
- MRC [MC_U105185857] Funding Source: UKRI
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Polymodal nociceptors detect noxious stimuli, including harsh touch, toxic chemicals and extremes of heat and cold. The molecular mechanisms by which nociceptors are able to sense multiple qualitatively distinct stimuli are not well understood. We found that the C. elegans PVD neurons are mulitidendritic nociceptors that respond to harsh touch and cold temperatures. The harsh touch modality specifically required the DEG/ENaC proteins MEC-10 and DEGT-1, which represent putative components of a harsh touch mechanotransduction complex. In contrast, responses to cold required the TRPA-1 channel and were MEC-10 and DEGT-1 independent. Heterologous expression of C. elegans TRPA-1 conferred cold responsiveness to other C. elegans neurons and to mammalian cells, indicating that TRPA-1 is a cold sensor. Our results suggest that C. elegans nociceptors respond to thermal and mechanical stimuli using distinct sets of molecules and identify DEG/ENaC channels as potential receptors for mechanical pain.
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