Peptidergic CGRPa Primary Sensory Neurons Encode Heat and Itch
and Tonically Suppress Sensitivity to Cold
Eric S. McCoy,1 Bonnie Taylor-Blake,1 Sarah E. Street,1 Alaine L. Pribisko,1 Jihong Zheng,1 and Mark J. Zylka1,* 1Department of Cell Biology and Physiology, UNC Neuroscience Center, The University of North Carolina at Chapel Hill, CB #7545, Chapel Hill, NC 27599, USA
*Correspondence: zylka@med.unc.edu
http://dx.doi.org/10.1016/j.neuron.2013.01.030
mmc1, 1-s2.0-S0896627313000962-main
SUMMARY
Calcitonin gene-related peptide (CGRP) is a classic molecular marker of peptidergic primary somatosen- sory 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 CGRPa-expressing sensory neurons reduced sensitivity to noxious heat, capsa- icin, and itch (histamine and chloroquine) and impaired thermoregulation but did not impair mecha- nosensation or b-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 CGRPa sensory neurons encode heat and itch and tonically cross-inhibit cold-respon- sive spinal neurons. Disruption of this crosstalk unmasks cold hypersensitivity, with mechanistic implications for neuropathic pain and temperature perception.
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