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Glucocorticoid-Potentiated Spinal Microglia Activation Contributes to Preoperative Anxiety-Induced Postoperative Hyperalgesia

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Abstract

Clinically, preoperative anxiety adversely affected postoperative hyperalgesia. As stress-induced glucocorticoids (GCs) were reported to sensitize the activation of microglia, the present study investigated whether and how GCs and microglia played in the process of preoperative anxiety-induced postoperative hyperalgesia. The study used an animal model that exposed rats to single prolonged stress (SPS) procedure to induce preoperative anxiety-like behaviors 24 h before the plantar incisional surgery. Behavioral testing revealed that preoperative SPS enhanced the mechanical allodynia induced by plantar incision. SPS was also found to induce elevated circulating corticosterone levels, potentiate the activation of spinal microglia, and increase the expression of spinal proinflammatory cytokines. Inhibition of microglia by pretreatment with minocycline attenuated the SPS-enhanced mechanical allodynia, and this was accompanied by decreased activation of spinal microglia and expression of proinflammatory cytokines. Another experiment was conducted by administering RU486, the GC receptor (GR) antagonist, to rats. The results showed that RU486 suppressed SPS-induced and SPS-potentiated proinflammatory activation of spinal microglia and revealed analgesic effects. Together, these data indicated that inhibition of stress-induced GR activation attenuated the preoperative anxiety-induced exacerbation of postoperative pain, and the suppression of spinal microglia activation may underlie this anti-hyperalgesia effect. Pending further studies, these findings suggested that GR and spinal microglia may play important roles in the development of preoperative anxiety-induced postoperative hyperalgesia and may serve as novel targets to prevent this phenomenon.

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    Authors and Affiliations

    1. Department of Anesthesiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China

      Rao Sun, Jinhua Bo, Hui Rong, Yishan Lei, Cui’e Lu, Bailing Hou, Yu’e Sun, Yue Liu, Zhengliang Ma & Xiaoping Gu

    2. Department of Anesthesiology, The First People’s Hospital of Lianyungang City, Lianyungang, Jiangsu, China

      Zhibin Zhao, Jiying Feng & Xiaobao Zhang

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    1. Rao Sun
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    Correspondence to Zhengliang Ma or Xiaoping Gu.

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    This research was supported by the National Natural Science Foundation of China (81471129, 81171048, 81171047) and a grant from the Department of Health of Jiangsu Province of China (XK201140, RC2011006).

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    Rao Sun and Zhibin Zhao contributed equally to this work.

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    Sun, R., Zhao, Z., Feng, J. et al. Glucocorticoid-Potentiated Spinal Microglia Activation Contributes to Preoperative Anxiety-Induced Postoperative Hyperalgesia. Mol Neurobiol 54, 4316–4328 (2017). https://doi.org/10.1007/s12035-016-9976-1

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