| First Author | Gölöncsér F | Year | 2021 |
| Journal | Br J Pharmacol | Volume | 178 |
| Issue | 23 | Pages | 4626-4645 |
| PubMed ID | 34363208 | Mgi Jnum | J:346619 |
| Mgi Id | MGI:7617180 | Doi | 10.1111/bph.15641 |
| Citation | Goloncser F, et al. (2021) Involvement of P2Y(12) receptors in a nitroglycerin-induced model of migraine in male mice. Br J Pharmacol 178(23):4626-4645 |
| abstractText | BACKGROUND AND PURPOSE: P2Y(12) receptors regulate different forms of pain and inflammation. In this study, we investigated the participation of P2Y(12) receptors in an animal model of migraine. EXPERIMENTAL APPROACH: We tested the effect of the centrally administered selective P2Y(12) antagonist PSB-0739 and P2Y(12) receptor gene (P2ry12(-/-) ) deficiency in acute nitroglycerin-treated mice. Additionally, platelet depletion was used to investigate the role of platelet P2Y(12) receptors during migraine-like pain. KEY RESULTS: Nitroglycerin induced sensory hypersensitivity of C57BL/6 wild-type (P2ry12(+/+) ) mice accompanied by an increase in c-fos and CGRP expression in the upper cervical spinal cord (C1-C2) and trigeminal nucleus caudalis. Similar changes were also observed in P2Y(12) gene-deficient (P2ry12(-/-) ) mice. Prophylactic intrathecal application of PSB-0739 reversed thermal hyperalgesia and head grooming time in wild-type mice but had no effect in P2ry12(-/-) mice. Furthermore, PSB-0739 was also effective when applied as a post-treatment. PSB-0739 administration suppressed the expression of c-fos in C1-C2 and trigeminal nucleus caudalis, and decreased the levels of dopamine and 5-hydroxytryptamine in C1-C2 in wild-type mice. Nitroglycerin treatment itself did not change adenosine diphosphate (ADP)-induced platelet activation measured by CD62P up-regulation in wild-type mice. Platelet depletion by anti-mouse CD41 antibody and clopidogrel attenuated nitroglycerin-induced thermal hypersensitivity and head grooming time in mice. CONCLUSION AND IMPLICATIONS: Our findings show that acute inhibition of P2Y(12) receptors alleviates migraine-like pain in mice by modulating the expression of c-fos and that platelet P2Y(12) receptors might contribute to this effect. Thus the blockade of P2Y(12) receptors may have therapeutic potential against migraine. |
