Objective: To determine the effect of preamputation pain on the behavioral response and astrocytic activation in the spinal cord of amputated rats, and to assess the association between preamputation pain and chronic amputation-related pain.Methods: A total of 84 adult male SD rats were randomly distributed into an NA group (?=42) and a PA group (n=42). The NA group was intraplantarly injected with saline 100 ^L, while the PA group was intraplantarly injected with complete Freund's adjuvant (CFA) 100 uL in both cases at 7 d before the amputation. Thermal withdrawal latency (TWL) was measured before the injection and at 1, 3, 5, and 7 d after the injection. All rats were amputated on the 7th day. The TWL, diet and water intake were measured on 1, 3, 5, 7, 10, 14, 17, 21, and 28 d after the amputation. Expression of glial fibrillary acidic protein (GFAP) in the L4-6 of spinal cord was measured by immunohistochemistry before the saline/ CFA injection, 7 d after the injection and 1, 3, 5, 7,10 d after the amputation..Results: The TWL significantly decreased on 1, 3, 5, and 7 d after the intraplantar administration of CFA compared with the basic value in the PA group (P<0.05), while there was no difference between 1, 3, 5, and 7 d after the intraplantar administration of saline and the basic value in the NA group (P>0.05). In addtions to the basic value, the TWL of the PA group was shorter than that of the NA group at the above-mentioned time-points (P<0.05). Compared with the preoperative level, the diet and water intake decreased significantly after the amputation in both groups, but recovered to the preoperative levels, by 3 d after the amputation in the NA group, and by 5 d after the amputation in the PA group. Compared with the TWL of the residual limb on the day of amputation, the TWL of the residual limb increased significantly 3 d after the amputation and remained elevated until 28 d after the amputation in the NA group (P<0.05), while there was no difference between each time point after the amputation and the day of the amputation in the PA group. Compared with the basic value, there was an obviously high expression of GFAP in the NA group beginning on the day of amputation and in the PA group 7 d after the CFA injection (P<0.05). After the amputation, the expression of GFAP was significantly higher in the PA group (P<0.0S).Conclusion: Preamputation pain delays the recovery and activates the spinal astrocytes which may turn the acute postoperative pain into a chronic one.%目的:观察截肢及截肢前疼痛刺激对截肢后大鼠行为学及脊髓背角浅层星型胶质细胞激活的影响,探讨截肢前疼痛对截肢术后疼痛发生的影响及其可能机制.方法:雄性SD大鼠84只,随机分为截肢前不致痛组(NA组,n=42)及截肢前致痛组(PA组,n=42).NA组和PA组于截肢前7d在左足足底皮下注射生理盐水100 μL或完全福氏佐剂(complete freund adjuvant,CFA) 100 μL,并均于第7天行截肢手术.观察截肢前、注射生理盐水/CFA后及截肢当天、截肢术后1,3,5,7,10,14,17,21,28 d大鼠饮食量、饮水量及左足/左残端热缩腿反射潜伏期(thermal withdrawal latency,TWL)的改变.在截肢前及致痛后7d、截肢后1,3,5,7,10d检测大鼠L4-6脊髓背角浅层胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)的表达情况.结果:PA组注射CFA后各观察时点左足足底TWL明显低于基础值(p＜0.05),NA组注射生理盐水后左足足底TWL值与基础值相比差异无统计学意义(p＞0.05),PA组各时点左足足底TWL值均低于NA组(P＜0.05).PA组注射CFA后第7天,脊髓背角浅层GFAP免疫阳性细胞与基础值相比明显增多(p＜0.05),NA组无明显改变.NA组和PA组截肢术后饮食、饮水量均较术前低,NA组于术后第3天,PA组于术后第5天饮食量、饮水量恢复至术前水平.与截肢当天相比,NA组于截肢术后第7天开始残端TWL值明显增高,直至术后第28天(P＜0.05),而PA组截肢术后残端各时点TWL值与截肢当天相比无明显变化(P＞0.05).NA组于截肢手术当天,PA组于注射CFA后第7天开始,脊髓GFAP阳性细胞数目与基础值相比明显增多(P＜0.05),且截肢后各观察时点PA组GFAP阳性细胞数目均明显高于NA组(P＜0.05).结论:术前患肢的疼痛导致脊髓背角星型胶质细胞的激活及截肢手术后大鼠饮食、饮水恢复延缓,可能使截肢术后急性期疼痛迁延为慢性疼痛,因而针对截肢手术前患肢的疼痛进行合理的镇痛十分必要.
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