BackgroundPostoperative pain (POP) is a severe acute pain encountered in patients suffering from an operation, and is less than adequately controlled by the currently available analgesics. Phosphatidylinositol 3-kinase (PI3K) has been reported to have an important role in neuropathic and inflammatory pain. Our previous research revealed that pre-surgical inhibition of spinal PI3K alleviated the pain behavior induced by plantar incision in mice. The aim of this study was to clarify whether post-surgical inhibition of PI3K would attenuate the POP and the underlying mechanisms.MethodsA POP model was established by plantar incision in Kunming mice. A behavioral test was performed to determine mechanical allodynia, thermal hyperalgesia, and cumulative pain scores. The spinal Fos was detected by immunohistochemistry. The spinal expression of protein kinase B (Akt) or phosphorylated Akt (pAkt) was explored using western blot. The cellular location of pAkt was determined by immunofluorescence.ResultsPost-surgical inhibition of PI3K attenuated mechanical allodynia, thermal hyperalgesia, and cumulative pain scores induced by plantar incision significantly in male mice, and mildly in female mice. Post-surgical inhibition of PI3K attenuated the expression of spinal Fos in male mice. Plantar incision induced a time-dependent expression of spinal pAkt in male mice, which was primarily expressed in the spinal dorsal horn, and localized with the neuron and microglia’s marker. Post-surgical inhibition of PI3K attenuated the activation of Akt induced by plantar incision in male mice as well.ConclusionsWe concluded that post-surgical inhibition of PI3K could attenuate the pain-related behaviors induced by plantar incision, by suppressing the activation of spinal Akt in male mice. This finding might be used in clinical studies to reach a better understanding of POP mechanisms and optimal treatment.

中文翻译：

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手术后抑制磷脂酰肌醇 3-激酶通过雄性小鼠脊髓 Akt 激活减轻足底切口诱导的术后疼痛行为

背景术后疼痛 (POP) 是手术患者遇到的严重急性疼痛，目前可用的镇痛药不能充分控制。据报道，磷脂酰肌醇 3-激酶 (PI3K) 在神经性和炎症性疼痛中具有重要作用。我们之前的研究表明，术前抑制脊髓 PI3K 减轻了小鼠足底切口引起的疼痛行为。本研究的目的是阐明术后抑制PI3K是否会减弱POP及其潜在机制。方法采用昆明小鼠足底切口建立POP模型。进行行为测试以确定机械性异常性疼痛、热痛觉过敏和累积疼痛评分。通过免疫组织化学检测脊髓Fos。使用蛋白质印迹研究蛋白激酶 B (Akt) 或磷酸化 Akt (pAkt) 的脊髓表达。pAkt 的细胞定位通过免疫荧光法确定。结果 PI3K 的术后抑制在雄性小鼠中显着减轻了机械性异常性疼痛、热痛觉过敏和足底切口引起的累积疼痛评分，而在雌性小鼠中则轻微。PI3K 的术后抑制减弱了雄性小鼠脊髓 Fos 的表达。足底切口诱导雄性小鼠脊髓 pAkt 的时间依赖性表达，其主要在脊髓背角表达，并定位于神经元和小胶质细胞的标记物。手术后抑制 PI3K 也减弱了雄性小鼠足底切口诱导的 Akt 活化。结论我们得出结论，手术后抑制 PI3K 可以通过抑制雄性小鼠脊髓 Akt 的激活来减轻足底切口诱导的疼痛相关行为。这一发现可用于临床研究，以更好地了解 POP 机制和最佳治疗。