硬膜外注射舒芬太尼和布托啡诺对骨癌痛大鼠神经行为功能的影响

Effect of butorphanol and sufentanil with epidural injections on neurobehavior function in bone cancer pain model rats

目的 观察硬膜外注射不同剂量的舒芬太尼或布托啡诺对骨癌痛大鼠神经功能及行为学的影响.方法 SD雌性未交配大鼠,体质量150～ 180 g,于L1～L2处行硬膜外置管,置管成功3d后,取无运动障碍的大鼠,采用Walker256乳腺癌细胞,建立胫骨癌痛模型或行假手术,共64只,按随机数字表法分为8组（n=8）：假手术组（C组）,骨癌痛生理盐水组（N组）,布托啡诺3组（B1组、B2组、B3组）,舒芬太尼3组（S1组、S2组、S3组）.癌痛模型建模成功后第10～14天,C组和N组硬膜外注射NS 30μl,B1组、B2组、B3组分别硬膜外注射30μl布托啡诺25,50,100 μg（溶于NS）,S1组、S2组、S3组硬膜外分别注射30μl舒芬太尼1,2,4μg（溶于NS）,1次/d.观察各组机械缩足反射阈值（mechanical withdrawal threshold,MWT）检测疼痛行为学的变化,并且通过各组行斜板试验和BBB（BASSO,BEATHE,BRESNAHAN）评分检测神经功能行为学的变化.结果 第1次给药前,各模型组[N组（15.23±2.46）g、B1组（16.14±2.28）g、B2组（15.42±3.22）g、B3组（14.35±2.32）g、S1组（15.37±2.11）g、S2组（15.22±2.93）g、S3组（16.25±2.36）g]和C组[（67.65±9.29）g]相比MWT水平明显降低,差异有统计学意义（P＜0.05）;与N组[（16.13±2.37）g]相比,B2组[（35.63±1.53）g]、B3组[（35.12±5.16）g]和S3组[（34.24±5.93）g]大鼠的MWT水平在第1次给药后明显升高,差异有统计学意义（P＜0.05）;第4次给药后6h,B3组大鼠的斜板实验[（34.72±4.56）°]和BBB评分[（10.64±1.82）分]与N组[（43.15±4.67）°,（14.05±1.78）分]相比明显降低,差异有统计学意义（P＜0.05）,但各模型组在第1次给药后BBB评分和斜扳试验差异无统计学意义（P＞0.05）.结论 布托啡诺50 μg或100μg或者舒芬太尼4μg硬膜外连续给药均可减轻大鼠骨癌痛,但布托啡诺100μg连续给药会损害骨癌痛大鼠神经功能,造成神经功能行为学影响.

Objective To observe the effect of different doses of butorphanol and sufentanil repeatedly epidural injected on the neurobehavior function in bone cancer model rats.Methods A PE-530 catheter was inserted into the epidural space of all male Sprague-Dawley rats（not mated,weighting 150-180 g） at L1-2 level.Three days after operation,64 rats without any motor dysfunction were randomly divided into eight groups （n=8）：sham operated group （group C）,normal saline with bone cancer pain group （group N）,butorphanol groups（group B 1,B2,B3）and sufentanil groups （group S1,S2,S3）.Bone cancer pain model was constructed in group N,B and S when rats in group C were sham operated.Rats in group C and N were epidurally injected NS 30μl each,and rats in group B1,B2 and B3 were respectively epidurally injected butorphanol 25,50,100 μg （all diluted to 30 μl with NS）,when rats in group S1,S2 and S3 were respectively cpidurally injected sufentanil 1,2,4 μg （all diluted to 30 μl with NS） on time per day for 10-14 days after modeling.The neurobehavior paw withdrawal threshold （MWT） of the left hind claw was recorded to observe the changes in pain behavior.The neurobehavior function of rats were recorded by BBB （BASSO,BEATTIE and BRESNAHAN） score and the inclined plane test.Results Compared with group C（（67.65±9.29） g）,the MWT of the model groups obviously decreased before the first time of injection （N （15.23± 2.46） g,B 1 （16.14±2.28） g,B2（15.42±3.22） g,B3（14.35±2.32） g,S1 （15.37±2.11）g,S2（15.22±2.93） g,S3（16.25± 2.36） g） （all P〈0.05））.Compared with group N（（16.13±2.37） g）,the MWT of group B2,B3 and S3 increased obviously after the first time of injection （（35.12±5.16） g,（35.63± 1.53） g and （34.24±5.93） g） （P〈 0.05）.At the first day of injection,there was no significant difference in the BBB scores and the inclined plane test between the model groups （P〉0.05）.At 6 h after the forth injection the inclined plane test and the BBB scores of group B3 were obviously decreased compared with group N （（34.72 ± 4.56） ° and （10.64 ± 1.82） points to （43.15±4.67）° and （14.05±1.78） points （P〈0.05））.Conclusion The results provide evidence that repeatedly epidural injection of butorphanol 50 μg or 100 μg or sufentanil 4 μg can reduce the pain of the rats with bone cancer pain.But repeated epidural injection of butorphanol 100 μg can injure the neurological function.