Dataset Information

Enhanced behavioral responses to cold stimuli following CGRP? sensory neuron ablation are dependent on TRPM8.

ABSTRACT:

Background

Calcitonin gene-related peptide-? (CGRP?) is a classic marker of peptidergic nociceptive neurons and is expressed in myelinated and unmyelinated dorsal root ganglia (DRG) neurons. Recently, we found that ablation of Cgrp?-expressing sensory neurons reduced noxious heat sensitivity and enhanced sensitivity to cold stimuli in mice. These studies suggested that the enhanced cold responses were due to disinhibition of spinal neurons that receive inputs from cold-sensing/TRPM8 primary afferents; although a direct role for TRPM8 was not examined at the time.

Results

Here, we ablated Cgrp?-expressing sensory neurons in mice lacking functional TRPM8 and evaluated sensory responses to noxious heat, cold temperatures, and cold mimetics (acetone evaporative cooling and icilin). We also evaluated thermoregulation in these mice following an evaporative cold challenge. We found that ablation of Cgrp?-expressing sensory neurons in a Trpm8-/- background reduced sensitivity to noxious heat but did not enhance sensitivity to cold stimuli. Thermoregulation following the evaporative cold challenge was not affected by deletion of Trpm8 in control or Cgrp?-expressing sensory neuron-ablated mice.

Conclusions

Our data indicate that the enhanced behavioral responses to cold stimuli in CGRP? sensory neuron-ablated mice are dependent on functional TRPM8, whereas the other sensory and thermoregulatory phenotypes caused by CGRP? sensory neuron ablation are independent of TRPM8.

SUBMITTER: McCoy ES

PROVIDER: S-EPMC4247560 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

Enhanced behavioral responses to cold stimuli following CGRPα sensory neuron ablation are dependent on TRPM8.

McCoy Eric S ES Zylka Mark J MJ

Molecular pain 20141119

<h4>Background</h4>Calcitonin gene-related peptide-α (CGRPα) is a classic marker of peptidergic nociceptive neurons and is expressed in myelinated and unmyelinated dorsal root ganglia (DRG) neurons. Recently, we found that ablation of Cgrpα-expressing sensory neurons reduced noxious heat sensitivity and enhanced sensitivity to cold stimuli in mice. These studies suggested that the enhanced cold responses were due to disinhibition of spinal neurons that receive inputs from cold-sensing/TRPM8 prim ...[more]

PMID: 25406633

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