Astrocytic P2X7 receptor in retrosplenial cortex drives electroacupuncture analgesia.

IF 3 4区医学 Q2 NEUROSCIENCES

Purinergic Signalling Pub Date : 2024-09-02 DOI:10.1007/s11302-024-10043-w

Wei Zhao, Si-Le Liu, Si-Si Lin, Ying Zhang, Chang Yu

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Abstract

P2X7 receptor (P2X7R) has been found to contribute to the peripheral mechanism of acupuncture analgesia (AA). However, whether it plays an important role in central mechanism remains unknown. In this study, we aimed to reveal the role of astrocytic P2X7R in retrosplenial cortex (RSC) in AA and provide new evidence for underlying the central mechanism of AA. We applied the chemogenetic receptors hM3Dq to stimulate or hM4Di to inhibit astrocytes ligand clozapine-N-oxide (CNO) following injection of adeno-associated virus (AAV) into the bilateral RSC, or pharmacologically intervened in the activity of the purinergic receptor P2X7R. Current data indicated that chemogenetic inhibition of astrocytes or injection of P2X7R agonist Bz-ATP in the bilateral RSC significantly reverses the analgesic effect of electroacupuncture (EA) in formalin tests while the bilateral injection of the P2X7R antagonist A438079 alleviated formalin-induced nociceptive behavior. Additionally, chemogenetic suppression of astrocytic P2X7R by injection of AAV in the bilateral RSC decreased hind paw flinches induced by formalin in the mice. These findings indicate the participation of both astrocytes and P2X7R in the RSC in EA analgesic. Moreover, P2X7R on astrocytes in the RSC appears to play a critical role in the ability of EA to attenuate formalin-induced pain responses in mice.

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后脾皮层星形胶质细胞 P2X7 受体驱动电针镇痛

研究发现，P2X7 受体（P2X7R）有助于针刺镇痛（AA）的外周机制。然而，它是否在中枢机制中发挥重要作用仍是未知数。本研究旨在揭示星形胶质细胞 P2X7R 在针刺镇痛中的作用，并为针刺镇痛的中枢机制提供新的证据。我们在双侧RSC注射腺相关病毒（AAV）后，应用化学遗传受体hM3Dq刺激或hM4Di抑制星形胶质细胞配体氯氮平-氧化物（CNO），或药物干预嘌呤能受体P2X7R的活性。目前的数据表明，化学抑制星形胶质细胞或在双侧RSC注射P2X7R激动剂Bz-ATP能显著逆转福尔马林试验中电针（EA）的镇痛效果，而双侧注射P2X7R拮抗剂A438079则能缓解福尔马林诱导的痛觉行为。此外，通过在双侧 RSC 注射 AAV 来化学抑制星形胶质细胞的 P2X7R，可减少福尔马林诱导的小鼠后爪退缩。这些发现表明，星形胶质细胞和 RSC 中的 P2X7R 都参与了 EA 镇痛。此外，RSC 星形胶质细胞上的 P2X7R 似乎在 EA 减轻福尔马林诱发的小鼠疼痛反应的能力中发挥了关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Purinergic Signalling 医学-神经科学

CiteScore

6.60

自引率

17.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.