Abstract
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.
Highlights
Purine receptors participate in peripheral and central sensitization and are associated with migraine headache
Previous studies showed that systemic administration of NTG induces hyperalgesia of the hindpaws, which is inhibited by the antimigraine drug sumatriptan in mice [14]
We report here that genetic deletion of P2X7 receptor (P2X7) (P2X7−/−) results in non-significant changes in the nociceptive threshold after NTG treatment, the selective P2X7 antagonist, Brilliant Blue G (BBG) completely prevents the effect of NTG in wild-type, but not in P2X7−/− mice and alleviates NTG-induced c-fos expression
Summary
Purine receptors participate in peripheral and central sensitization and are associated with migraine headache. Previous studies showed that systemic administration of NTG induces hyperalgesia of the hindpaws, which is inhibited by the antimigraine drug sumatriptan in mice [14] These observations validate extrafacial thermal and mechanical hyperalgesia as a potential behavioural correlate of migraine in mice subjected to NTG. Chemical activation of the C-fibers of the trigeminal nerve - leading to transmission of nociceptive information into the brainstem - induces c-fos expression within specific areas of the TNC. This is inhibited by anti-migraine therapeutics, such as olcegepant [17]. These findings indicate that those drugs, which influence c-fos expression in the TNC might have relevance in the mediation of potential anti-migraine effects
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