p-CREB在切割疼痛大鼠脊髓背角的变化

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。

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

ObjectiveTo explore the role of phosphorylation of cAMP response element binding protein (CREB) in the incision-induced pain hypersensitivity. MethodsA 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. ResultsAfter the hind-paw incision, phosphorylation of CREB was enhanced in the ipsilateral lumbar spinal cord(P＜0.05). 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(P＞0.05). Gabapentin didn’t inhibit the phosphorylation of CREB(P＜0.05) but partly inhibited the mechanical allodynia. ConclusionIncision 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.