title: Effect of genetic deletion and pharmacological antagonism of P2X7 receptors in a mouse animal model of migraine.
abstract: BACKGROUND
  Purine receptors participate in peripheral and central sensitization and are associated with migraine headache. We investigated the role of P2X7 receptor (P2X7) in a nitroglycerin (NTG)-induced mouse model of migraine.
  
  
  METHODS
  Intraperitoneal NTG injection (15 mg/kg) triggered thermal hyperalgesia in the hindpaws of wild-type C57BL/6J mice, followed by the induction of c-fos in upper cervical spinal cord and trigeminal nucleus caudalis. The effect of genetic deletion of P2X7 and the selective P2X7 antagonist Brilliant Blue G (BBG) were examined on hyperalgesia and c-fos induction.
  
  
  RESULTS
  NTG decreased the paw withdrawal threshold in both wild-type and P2X7 knockout mice. Nevertheless, subacute BBG treatment (50 mg/kg/day i.p.) completely prevented the effect of NTG in wild-type, but not in knockout mice. Whereas P2X7 deficiency differentially affected the expression of c-fos, the average number of fos-immuno-reactive neurons in trigeminal nucleus caudalis, but not in upper cervical spinal cord was lower in BBG-treated wild-type mice after NTG treatment.
  
  
  CONCLUSIONS
  Our results show that P2X7 receptors might participate in the pathogenesis of migraine, although upregulation of other P2X receptors probably compensate for the loss of its action in knockout mice. The data also suggest the therapeutic potential of P2X7 antagonists for the treatment of migraine.
authors.forename: Flóra
authors.initials: F
authors.lastname: Gölöncsér
authors.affiliation: Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083, Budapest, Szigony u,, 43, Hungary. sperlagh@koki.hu.
authors.forename: Beáta
authors.initials: B
authors.lastname: Sperlágh
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008881:Migraine Disorders / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D058486:Receptors, Purinergic P2X7 / Q000172:deficiency* / Q000235:genetics*
chemical_list: D058920:Purinergic P2X Receptor Antagonists; D058486:Receptors, Purinergic P2X7