小胶质细胞 P2Y14 受体在反复炎症性硬脑膜刺激后导致中枢敏化。
Microglial P2Y14 receptor contributes to central sensitization following repeated inflammatory dural stimulation.
机构信息
Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, China.
Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
出版信息
Brain Res Bull. 2021 Dec;177:119-128. doi: 10.1016/j.brainresbull.2021.09.013. Epub 2021 Sep 17.
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.
背景
最近的研究表明，脊髓小胶质细胞中的 P2Y 受体在神经病理性和炎症性疼痛的发展中起作用。然而，小胶质细胞中的 P2Y 受体是否参与偏头痛的发病机制尚不清楚。因此，本研究旨在探讨三叉颈复合体（TCC）中小胶质细胞 P2Y14 受体在偏头痛中的作用。
方法
我们使用反复硬脑膜炎性刺激诱导的偏头痛大鼠模型，通过 Western Blotting 和免疫荧光染色检测偏头痛大鼠 TCC 中 P2Y14 受体的表达。然后，我们测定了 P2Y14 拮抗剂 PPTN 对炎性汤（IS）诱导的 TCC 机械性痛觉过敏、小胶质细胞激活和 ERK 表达的影响。
结果
硬脑膜反复 IS 刺激 4 或 7 天后，TCC 中小胶质细胞中 P2Y14 受体的表达水平显著增加。PPTN 的应用显著减轻了偏头痛模型大鼠眶周疼痛阈值的降低。此外，硬脑膜反复 IS 刺激诱导 TCC 中小胶质细胞的激活和 ERK1/2 的磷酸化，PPTN 的应用消除了这种作用。
结论
我们的研究结果表明，TCC 中小胶质细胞中 P2Y14 受体的增加在偏头痛大鼠模型机械性痛觉过敏的产生中起关键作用。此外，P2Y14 受体的激活还涉及小胶质细胞的激活和 ERK 磷酸化。小胶质细胞中的 P2Y14 受体可能作为偏头痛治疗的潜在靶点。
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