title: Enhanced behavioral responses to cold stimuli following CGRPα sensory neuron ablation are dependent on TRPM8.
abstract: BACKGROUND
  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 primary afferents; although a direct role for TRPM8 was not examined at the time.
  
  
  RESULTS
  Here, we ablated Cgrpα-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 Cgrpα-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 Cgrpα-expressing sensory neuron-ablated mice.
  
  
  CONCLUSIONS
  Our data indicate that the enhanced behavioral responses to cold stimuli in CGRPα sensory neuron-ablated mice are dependent on functional TRPM8, whereas the other sensory and thermoregulatory phenotypes caused by CGRPα sensory neuron ablation are independent of TRPM8.
authors.forename: Eric S
authors.initials: ES
authors.lastname: McCoy
authors.affiliation: Department of Cell Biology and Physiology, UNC Neuroscience Center, The University of North Carolina, CB #7545, Chapel Hill, North Carolina 27599, USA. zylka@med.unc.edu.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Zylka
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects / Q000235:genetics; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D015740:Calcitonin Gene-Related Peptide / Q000172:deficiency* / Q000235:genetics; D002452:Cell Count; D003080:Cold Temperature / Q000009:adverse effects*; D004167:Diphtheria Toxin / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016900:Neurofilament Proteins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011744:Pyrimidinones / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000378:metabolism*; D012684:Sensory Thresholds / Q000187:drug effects*; D050053:TRPM Cation Channels / Q000378:metabolism*
chemical_list: D004167:Diphtheria Toxin; D066257:Heparin-binding EGF-like Growth Factor; D016900:Neurofilament Proteins; D011744:Pyrimidinones; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; C051774:neurofilament protein H; C490483:icilin; D010751:Phosphopyruvate Hydratase; D015740:Calcitonin Gene-Related Peptide