title: Meningeal transient receptor potential channel M8 activation causes cutaneous facial and hindpaw allodynia in a preclinical rodent model of headache.
abstract: BACKGROUND
  Migraine headache is a neurological disorder affecting millions worldwide. However, little is known about the mechanisms contributing to migraine. Recent genome-wide association studies have found single nucleotide polymorphisms in the gene encoding transient receptor potential channel M8. Transient receptor potential channel M8 is generally known as a cold receptor but it has been implicated in pain signaling and may play a role in migraine pain.
  
  
  METHODS
  In order to investigate whether transient receptor potential channel M8 may contribute to the pain of migraine, the transient receptor potential channel M8 activator icilin was applied to the dura mater using a rat behavioral model of headache. Cutaneous allodynia was measured for 5 hours using Von Frey filaments.
  
  
  RESULTS
  Dural application of icilin produced cutaneous facial and hind paw allodynia that was attenuated by systemic pretreatment with the transient receptor potential channel M8-selective antagonist AMG1161 (10 mg/kg p.o.). Further, the anti-migraine agent sumatriptan (0.6 mg/kg s.c.) or the non-selective NOS inhibitor L-NAME (20 mg/kg i.p.) also attenuated allodynia when given as a pretreatment.
  
  
  CONCLUSIONS
  These data indicate that transient receptor potential channel M8 activation in the meninges produces behaviors in rats that are consistent with migraine and that are sensitive to pharmacological mechanisms known to have efficacy for migraine in humans. The findings suggest that activation of meningeal transient receptor potential channel M8 may contribute to the pain of migraine.
authors.affiliation: Department of Pharmacology, University of Arizona, USA.
authors.forename: Carolina C
authors.initials: CC
authors.lastname: Burgos-Vega
authors.affiliation: Department of Pharmacology, University of Arizona, USA.
authors.forename: David Dong-Uk
authors.initials: DD
authors.lastname: Ahn
authors.affiliation: Department of Pharmacology, University of Arizona, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Bischoff
authors.affiliation: Amgen Inc., USA.
authors.forename: Weiya
authors.initials: W
authors.lastname: Wang
authors.affiliation: Amgen Inc., USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Horne
authors.affiliation: Amgen Inc., USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Wang
authors.affiliation: Amgen Inc., USA.
authors.forename: Narender
authors.initials: N
authors.lastname: Gavva
authors.affiliation: Department of Pharmacology, University of Arizona, USA School of Behavioral and Brain Sciences, University of Texas at Dallas, USA gregory.dussor1@utdallas.edu.
authors.forename: Gregory
authors.initials: G
authors.lastname: Dussor
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008881:Migraine Disorders / Q000378:metabolism / Q000503:physiopathology*; D011744:Pyrimidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050053:TRPM Cation Channels / Q000378:metabolism*
chemical_list: D011744:Pyrimidinones; D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat; C490483:icilin
keywords: Transient receptor potential channel M8; allodynia; cold; dura; headache; migraine; sumatriptan