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.
