Neuronal GRK2 regulates microglial activation and contributes to electroacupuncture analgesia on inflammatory pain in mice.
Neuronal GRK2 regulates microglial activation and contributes to electroacupuncture analgesia on inflammatory pain in mice.
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神经元GRK2调节小胶质细胞激活并有助于电针镇痛小鼠炎症痛
DOI：
10.1186/s40659-022-00374-6
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发表时间：
2022-02-03
影响因子：
6.7
通讯作者：
Mao-Ying QL
中科院分区：
文献类型：
--
作者：
Chen Y;Zhou Y;Li XC;Ma X;Mi WL;Chu YX;Wang YQ;Mao-Ying QL
蛋白偶联受体激酶2 （GRK2）已被证明在慢性疼痛的发展中起着至关重要的作用。针灸是一种替代疗法，广泛用于疼痛管理。在这项研究中，我们研究了脊髓神经元GRK2在电针镇痛中的作用。方法后爪足底表面皮下注射完全弗氏佐剂（CFA），建立小鼠炎性疼痛模型。采用von Frey试验检测小鼠的机械异常性痛。小鼠经电针（BL60和ST36穴）治疗1周。通过脊髓内注射含有神经元特异性启动子的腺相关病毒（AAV）实现脊髓神经元GRK2的过表达和下调，并通过实时PCR评估小胶质细胞的激活和神经炎症。结果足底注射CFA诱导小鼠脊髓GRK2和小胶质细胞活性降低，并伴有神经炎症。EA治疗增加了脊柱GRK2，减少了神经炎症，并显著减少了cfa引起的机械异常性痛。脊髓GRK2的非细胞特异性下调明显削弱了EA的作用。此外，椎管内注射含有神经元特异性启动子的AAV特异性下调神经元GRK2，减弱EA对cfa诱导的机械性异常痛和小胶质细胞激活的调节作用。同时，脊髓神经元GRK2的过表达减少了机械异常性疼痛。这些都表明，神经元GRK2介导了小胶质细胞的激活和神经炎症，并随后促进了cfa诱导的炎症性疼痛。结论脊髓GRK2的恢复及其对小胶质细胞活化和神经炎症的抑制可能是EA镇痛的重要机制。我们的研究结果进一步提示脊柱GRK2，特别是神经元GRK2可能是EA镇痛和疼痛管理的潜在靶点，我们为EA治疗疼痛提供了新的实验依据。
BackgroundG protein coupled receptor kinase 2 (GRK2) has been demonstrated to play a crucial role in the development of chronic pain. Acupuncture is an alternative therapy widely used for pain management. In this study, we investigated the role of spinal neuronal GRK2 in electroacupuncture (EA) analgesia.MethodsThe mice model of inflammatory pain was built by subcutaneous injection of Complete Freund’s Adjuvant (CFA) into the plantar surface of the hind paws. The mechanical allodynia of mice was examined by von Frey test. The mice were subjected to EA treatment (BL60 and ST36 acupuncture points) for 1 week. Overexpression and downregulation of spinal neuronal GRK2 were achieved by intraspinal injection of adeno associated virus (AAV) containing neuron-specific promoters, and microglial activation and neuroinflammation were evaluated by real-time PCR.ResultsIntraplantar injection with CFA in mice induced the decrease of GRK2 and microglial activation along with neuroinflammation in spinal cord. EA treatment increased the spinal GRK2, reduced neuroinflammation, and significantly decreased CFA-induced mechanical allodynia. The effects of EA were markedly weakened by non-cell-specific downregulation of spinal GRK2. Further, intraspinal injection of AAV containing neuron-specific promoters specifically downregulated neuronal GRK2, and weakened the regulatory effect of EA on CFA-induced mechanical allodynia and microglial activation. Meanwhile, overexpression of spinal neuronal GRK2 decreased mechanical allodynia. All these indicated that the neuronal GRK2 mediated microglial activation and neuroinflammation, and subsequently contributed to CFA-induced inflammatory pain.ConclusionThe restoration of the spinal GRK2 and subsequent suppression of microglial activation and neuroinflammation might be an important mechanism for EA analgesia. Our findings further suggested that the spinal GRK2, especially neuronal GRK2, might be the potential target for EA analgesia and pain management, and we provided a new experimental basis for the EA treatment of pain.
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DOI：
10.1155/2015/848603
发表时间：
2015
期刊：
Evidence-based complementary and alternative medicine : eCAM
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作者：
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DOI：
10.1002/ejp.1336
发表时间：
2019-04
期刊：
European journal of pain (London, England)
影响因子：
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