Peptidergic CGRPα Primary Sensory Neurons Encode Heat and Itch and Tonically Suppress Sensitivity to Cold

被引:204
作者
McCoy, Eric S. [1 ]
Taylor-Blake, Bonnie [1 ]
Street, Sarah E. [1 ]
Pribisko, Alaine L. [1 ]
Zheng, Jihong [1 ]
Zylka, Mark J. [1 ]
机构
[1] Univ N Carolina, Dept Cell Biol & Physiol, UNC Neurosci Ctr, Chapel Hill, NC 27599 USA
关键词
PRIMARY AFFERENT NEURONS; RECEPTOR POTENTIAL VANILLOID-1; MOUSE GLABROUS SKIN; SUBSTANTIA-GELATINOSA; BEHAVIORAL-RESPONSES; NOCICEPTIVE NEURONS; SPINAL-CORD; PAIN; TRPM8; CAPSAICIN;
D O I
10.1016/j.neuron.2013.01.030
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 CGRP alpha-expressing sensory neurons reduced sensitivity to noxious heat, capsaicin, and itch (histamine and chloroquine) and impaired thermoregulation but did not impair mechanosensation or beta-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 CGRP alpha 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.
引用
收藏
页码:138 / 151
页数:14
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