p-CREB在切割疼痛大鼠脊髓背角的变化

Change of p-CREB after surgical incisional pain in rat spinal cord

目的:探讨环磷酸腺苷反应元件结合蛋白(cAMP response element binding protein,p-CREB)在切割痛敏形成中的作用。方法:异氟烷麻醉大鼠后切割后足。免疫组织化学染色,荧光双标对p-CREB进行定位。腹腔注射吗啡和加巴喷丁,进行行为学测定和免疫组织化学染色。结果:大鼠后足切割痛可以使同侧腰段脊髓背角内p-CREB增加,切割后0.5～3 h内比较明显(P<0.05)。p-CREB增加主要定位于背角神经元。腹腔注射吗啡产生镇痛作用的同时,与未切割组相比,p-CREB没有出现增加(P>0.05)。加巴喷丁产生部分镇痛作用时,与未切割组相比,p-CREB增加(P<0.05)。结论:切割疼痛所致的同侧脊髓背角内p-CREB增加与切割疼痛和痛觉过敏密切相关。吗啡对切割疼痛的镇痛作用机制与抑制脊髓背角内CREB的磷酸化增加有关。加巴喷丁对切割疼痛的镇痛作用机制与抑制脊髓背角内CREB磷酸化关系不密切。

Objective To explore the role of phosphorylation of cAMP response element binding protein（CREB） in the incision-induced pain hypersensitivity.Methods A longitudinal incision was made in one plantar hind paw of isoflurane-anesthetized rats.Spinal cords were removed at various postoperative time after behavior test.Phosphorylation of CREB was determined by immunohistochemistry and double-labeling immunofluorescence.Morphine and gabapentin were intraperitoneally injected before the behavior test and were used to determine the interaction between phosphorylation of CREB and morphine and gabapentin.Results After the hind-paw incision,phosphorylation of CREB was enhanced in the ipsilateral lumbar spinal cord（P0.05）.The enhancement of p-CREB was mainly in the neurons in the dorsal horn of the spinal cord.All these were shown by double-labeling technique and p-CREB was mainly in the neurons.Intraperitoneal injection of morphine prevented the increased phosphorylation of CREB in the spinal cord and inhibited the mechanical allodynia induced by the incision（P0.05）.Gabapentin didn＇t inhibit the phosphorylation of CREB（P0.05） but partly inhibited the mechanical allodynia.Conclusion Incision induces the phosphorylation of CREB in the spinal cord,and the increase of p-CREB is mainly in the neurons.Phosphorylation of CREB in the spinal cord contributes to the pain hypersensitivity induced by surgical incision.