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首页> 美国卫生研究院文献>The FASEB Journal >Impaired sensitivity to pain stimuli in plasma membrane calcium ATPase 2 (PMCA2) heterozygous mice: a possible modality- and sex-specific role for PMCA2 in nociception
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Impaired sensitivity to pain stimuli in plasma membrane calcium ATPase 2 (PMCA2) heterozygous mice: a possible modality- and sex-specific role for PMCA2 in nociception

机译：质膜ATPase 2（PMCA2）杂合小鼠对疼痛刺激的敏感性受损：PMCA2在伤害感受中的可能模式和性别特异性作用

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Plasma membrane calcium ATPase 2 (PMCA2) is a calcium pump that plays important roles in neuronal function. Although it is expressed in pain-associated regions of the CNS, including in the dorsal horn (DH), its contribution to pain remains undefined. The present study assessed the role of PMCA2 in pain responsiveness and the link between PMCA2 and glutamate receptors, GABA receptors (GABARs), and glutamate transporters that have been implicated in pain processing in the DH of adult female and male PMCA2+/+ and PMCA2+/− mice. Behavioral assays evaluated mechanical and thermal pain responsiveness. Mechanical sensitivity was significantly increased by 52% and heat sensitivity was reduced by 29% in female, but not male, PMCA2+/− mice compared with PMCA2+/+ controls. There were female-specific changes in metabotropic glutamate receptor 1, NMDA receptor 2A, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR1, GABABR1, and GABABR2 levels, whereas metabotropic glutamate receptor 5, NMDA receptor 2B, GluR2, and GABAARα2 levels were not altered. Glutamate aspartate transporter levels were higher and glial glutamate transporter 1 levels were lower in the DH of female, but not male, PMCA2+/− mice. These findings indicate a novel role for PMCA2 in modality- and sex-dependent pain responsiveness. Female-specific molecular changes potentially account for the altered pain responses.—Khariv, V., Ni, L., Ratnayake, A., Sampath, S., Lutz, B. M., Tao, X.-X., Heary, R. F., Elkabes, S. Impaired sensitivity to pain stimuli in plasma membrane calcium ATPase 2 (PMCA2) heterozygous mice: a possible modality- and sex-specific role for PMCA2 in nociception.
机译：质膜钙ATPase 2（PMCA2）是一种钙泵，在神经元功能中起重要作用。尽管它在中枢神经系统的疼痛相关区域表达，包括在背角（DH）中表达，但其对疼痛的作用仍然不确定。本研究评估了PMCA2在疼痛反应中的作用以及PMCA2与谷氨酸受体，GABA受体（GABARs）和谷氨酸转运蛋白之间的联系，这些谷氨酸受体与成年雌性和雄性PMCA2 + // + 和PMCA2 +/- 小鼠。行为分析评估了机械和热痛反应。与PMCA2 + / + 对照相比，雌性（而非雄性）PMCA2 +/- 小鼠的机械敏感性显着提高了52％，而热敏感性降低了29％。代谢型谷氨酸受体1，NMDA受体2A，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚基GluR1，GABABR1和GABABR2的水平有女性特异性变化，而代谢型谷氨酸受体5，NMDA受体则有变化。 2B，GluR2和GABAARα2水平未改变。雌性（而非雄性）PMCA2 +/- 小鼠的DH中，谷氨酸谷氨酸转运蛋白水平较高，而胶质谷氨酸转运蛋白1水平较低。这些发现表明PMCA2在模态和性别依赖性疼痛反应中具有新作用。女性特有的分子变化可能是造成疼痛反应改变的原因。—Khariv，V.，Ni，L.，Ratnayake，A.，Sampath，S.，Lutz，BM，Tao，X.-X.，Heary，RF， Elkabes，S.对质膜ATPase 2（PMCA2）杂合小鼠的疼痛刺激的敏感性受损：PMCA2在伤害感受中的可能模式和性别特异性作用。

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