Microglial P2Y14 receptor contributes to central sensitization following repeated inflammatory dural stimulation.

BACKGROUND: Recent studies have indicated that P2Y receptors in spinal microglia play a role in the development of neuropathic and inflammatory pain. However, it remains unclear whether P2Y receptors in microglia are involved in the pathogenesis of migraine. Therefore, the aim of this study was to investigate the role of microglial P2Y14 receptor in trigeminal cervical complex (TCC) in migraine. METHODS: We used a rat model of migraine induced by repeated inflammatory stimulation of the dura and examined the expression of P2Y14 receptor in the TCC in migraine rats by Western Blotting and immunofluorescence staining. Then, we determined the effect of P2Y14 antagonist PPTN on inflammatory soup (IS)-induced mechanical allodynia, microglial activation and ERK expression in TCC. RESULTS: The expression level of P2Y14 receptor increased significantly in microglia in TCC after 4 or 7 days of repeated IS stimulation of the dura. Application of PPTN significantly attenuated the decrease of periorbital pain threshold in migraine model rats. In addition, repeated IS stimulation of the dura induced the activation of microglia and the phosphorylation of the ERK1/2 in microglia in TCC, which were abolished by the application of PPTN. CONCLUSION: Our findings suggest that the increased P2Y14 receptor in microglia in TCC play a crucial role in the generation of mechanical allodynia in migraine rat model. Furthermore, the activation of the P2Y14 receptor is involved in microglial activation and ERK phosphorylation as well. The P2Y14 receptor in microglia might be used as a potential target for migraine treatment.

Association of the cyclooxygenase-2 1759A allele with migraine in Chinese Han individuals.

Cyclooxygenase-2 (COX-2) is known to be involved in the pathogenesis of migraine, and some polymorphisms are known to affect the expression of COX-2. This retrospective case-control study aimed to explore the associations between the -765 G>C (rs20417), -1759 G>A (rs3218625), and -8473 C>T (rs5275) COX-2 polymorphisms and migraine in Chinese Han individuals. One hundred and ten unrelated Han Chinese patients with migraine and 108 healthy controls were recruited between 03/2014 and 08/2016 at the First Affiliated Hospital of Nanjing Medical University and the First People's Hospital of Lianyungang City. The genotypes of all polymorphisms in controls followed the Hardy-Weinberg equilibrium (P = 0.215, P = 0.884, and P = 0.689). There were differences in the genotype and allele distributions of the COX-2-1759G>A (Gly587Arg) polymorphism between the migraine and control groups (P = 0.038 and P = 0.040, respectively). Compared with the COX-2-1759AG genotype, GG genotype carriers had an increased risk of migraine (odds ratio (OR) = 8.720, 95% confidence interval (CI): 1.072-70.960, P = 0.038). The frequency of the COX-2-1759A allele in patients with migraine was significantly lower than the controls (OR = 0.119, 95%CI: 0.015-0.957, P = 0.040). Adjusted age and sex, a statistical difference was found in the dominant model of COX-2-1759 G>A (OR = 0.118, 95% CI 0.014 to 0.962, P = 0.046). No significant difference was detected regarding the -765G>C and -8473T>C polymorphisms between the two groups. The COX-2 1759A allele might be involved in the development of migraine in Chinese Han individuals, but this will have to be confirmed in large-scale studies.