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

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.