Neuron
Volume 78, Issue 1, 10 April 2013, Pages 138-151
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Article
Peptidergic CGRPα Primary Sensory Neurons Encode Heat and Itch and Tonically Suppress Sensitivity to Cold

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Summary

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.

Highlights

► CGRPα DRG neurons are required to sense heat and some pruritogens ► Cold sensation is enhanced after ablating CGRPα neurons in adult mice ► CGRPα afferents tonically cross-inhibit cold/icilin-responsive spinal neurons ► CGRPα primary sensory neurons contribute to thermoregulation and cold defense

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