Effect of genetic deletion and pharmacological antagonism of P2X7 receptors in a mouse animal model of migraine

The Journal of Headache and Pain

Research Article

Beáta Sperlágh¹  Flóra Gölöncsér² 

[1] Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Szigony u., 43, H-1083, Hungary;Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Szigony u., 43, H-1083, Hungary;János Szentágothai School of Neurosciences, Semmelweis University School of Ph.D Studies, Budapest, Hungary;

关键词: P2X7 receptor;    Brilliant blue G;    nitroglycerin;    mouse model;    migraine;   

DOI  :  10.1186/1129-2377-15-24

 received in 2014-01-30, accepted in 2014-04-15,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundPurine 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.MethodsIntraperitoneal 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.ResultsNTG 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© Gölöncsér and Sperlágh; licensee Springer. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.