Peptidergic CGRPα primary sensory neurons encode heat and itch and tonically suppress sensitivity to cold.
| Autor: | McCoy ES; Department of Cell Biology and Physiology, UNC Neuroscience Center, The University of North Carolina at Chapel Hill, CB #7545, Chapel Hill, NC 27599, USA., Taylor-Blake B, Street SE, Pribisko AL, Zheng J, Zylka MJ |
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| Jazyk: | angličtina |
| Zdroj: | Neuron [Neuron] 2013 Apr 10; Vol. 78 (1), pp. 138-51. Date of Electronic Publication: 2013 Mar 21. |
| DOI: | 10.1016/j.neuron.2013.01.030 |
| Abstrakt: | Calcitonin gene-related peptide (CGRP) is a classic molecular marker of peptidergic primary somatosensory neurons. Despite years of research, it is unknown whether these neurons are required to sense pain or other sensory stimuli. Here, we found that genetic ablation of CGRPα-expressing sensory neurons reduced sensitivity to noxious heat, capsaicin, and itch (histamine and chloroquine) and impaired thermoregulation but did not impair mechanosensation or β-alanine itch-stimuli associated with nonpeptidergic sensory neurons. Unexpectedly, ablation enhanced behavioral responses to cold stimuli and cold mimetics without altering peripheral nerve responses to cooling. Mechanistically, ablation reduced tonic and evoked activity in postsynaptic spinal neurons associated with TRPV1/heat, while profoundly increasing tonic and evoked activity in spinal neurons associated with TRPM8/cold. Our data reveal that CGRPα sensory neurons encode heat and itch and tonically cross-inhibit cold-responsive spinal neurons. Disruption of this crosstalk unmasks cold hypersensitivity, with mechanistic implications for neuropathic pain and temperature perception. (Copyright © 2013 Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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