p38MAPK信号通路在大鼠幻肢痛中的作用

目的：探讨p38MAPK信号通路在患有幻肢痛的大鼠脊髓和背根神经节内的激活情况，以及给予特异抑制剂后的影响。方法：取健康成年雄性SD大鼠(n=48)麻醉下行一侧坐骨神经横断术建立幻肢痛模型，同时另取同窝健康大鼠作为假手术组(S组，n=24)。术后观察大鼠咬噬情况，并进行咬噬评分。将成模后的幻肢痛大鼠随机分成2组：幻肢痛组(P组，n=24)和幻肢痛p38MAPK通路抑制剂组(P+I组，n=24)。成模后的每周一，P+I组大鼠静脉注射p38MAPK抑制剂SB203580 0.8 mg/kg，其余组静脉注射等量的生理盐水。于给药后第4周末(T1)、第6周末(T2)和第8周末(T3)分别从各组中随机取8只大鼠，分别检测脊髓和背根神经节(DRG)的磷酸化p38MAPK(P-p38MAPK)水平。结果：与S组比较，成模的幻肢痛组大鼠自术后第2天开始陆续发生咬噬，咬噬评分8~11分；在给予抑制剂后，P+I组的咬噬评分有所下降。与S组相比，P组和P+I组大鼠P-p38MAPK水平明显升高(P<0.05或P<0.01)；与P组比较，P+I组P-p38MAPK的表达水平明显降低(P<0.05或P<0.01)。结论：p38MAPK信号通路参与大鼠幻肢痛的疼痛的调控。

Role of p38MAPK signaling pathway in rats with phantom limb pain

Objective: To investigate the role of p38MAPK signal pathway in spinal cord and dorsal rootganglion (DRG) in rats with phantom limb pain and the eff ects of specifi c inhibitors.Methods: Healthy adult male SD rats (n=48) were cut off one side of the sciatic under anesthesiato establish a model of phantom limb pain. In addition, the healthy rats were taken as a sham group(group S, n=24). The animals were scored by observing the action of chewing (0=no chewing,13=the worst chewing) after the operation and were sacrificed on the following day after theoperation. The successful model of phantom limb pain were randomly divided into 2 groups: aphantom limb pain group (group P, n=24) and a phantom limb pain plus inhibitor group (groupP+I, n=24). SB203580 was given to the rat at 0.8 mg/kg on every Monday until the rats weresacrificed, the rest of the rats received an equal amount of saline. Eight rats from each group wererandomly taken for the determination of levels of P-p38MAPK in spinal cord and DRG beforeadministration and on the 4th, 6th, 8th weekend following the administration, respectively.Results: In the sham group, no animal developed chewing. Meanwhile, rats in successful modelof phantom limb pain group began chewing from the 2nd day after operation with scores at eightto eleven. The chewing scores in the P+I group were reduced after the treatment. Compared withgroup S, P-p38MAPK levels were elevated in groups of P and P+I (P<0.05 or P<0.01). Comparedwith group P, P-p38MAPK level was decreased in the group P+I (P<0.05 or P<0.01).Conclusion: P38MAPK signal pathway involves in the development of phantom limb pain.