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.
Read the paper
Related studies
- Calcium Ions in the Physiology and Pathology of the Central Nervous System
- AI-powered in silico twins: redefining precision medicine through simulation, personalization, and predictive healthcare
- In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene
- In Silico drug repurposing pipeline using deep learning and structure based approaches in epilepsy
- Targeting serotonin receptors with phytochemicals – an in-silico study
- In silico exploration of anti-prostate cancer compounds from differential expressed genes
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.