加巴喷丁减轻骨癌痛大鼠的机械痛敏

Gabapentin reduces mechanical allodynia in a rat model of tibial bone cancer pain

目的 观察不同剂量加巴喷丁对胫骨癌痛大鼠机械痛敏的影响.方法 雌性SD大鼠42只,随机分为7组（n=6）,即空白对照组（N组）、假手术＋生理盐水组（SN组）、假手术＋加巴喷丁200 mg ·kg-1·d-1组（SG200组）、骨癌痛＋生理盐水组（BN组）、骨癌痛＋加巴喷丁50mg·kg^-1·d^-1组（BG50组）、骨癌痛＋加巴喷丁100mg·kg^-1·d^-1组（BG100组）和骨癌痛＋加巴喷丁200mg· kg-1·d-1组（BG200组）.从术后第7天起,在保持正常饮水量的前提下,SG200组、BG50组、BG100组和BG200组每天分别按体重将加巴喷丁200mg/kg、50 mg/kg、100 mg/kg、200 mg/kg溶于5 ml生理盐水中饲喂,N组、SN 组和BN组仅给予同等量的生理盐水.分别在术前、术后1,3,5,7d和8,10,12,14d（分别对应为给药后1,3,5,7d）测定右后肢机械缩足阈值（MWT）和自由行走痛行为评分.结果 术后第7天,骨癌痛大鼠MWT [ （3.78 ±0.38）g]和自由行走痛评分[（0.76 ±0.44）分]与空白对照组[（14.50 ±1.38）g,（0.00±0.00）分]和假手术组[（10.21±0.88）g,（0.00±0.00）分]比较,差异具有统计学意义（P＜0.05）.在连续应用加巴喷丁的1周中,SN组和SG200组大鼠行为学的差异无统计学意义（P＞0.05）; BG50组与BN组比较,MWT无明显差异（P＞0.05）,自由行走痛行为评分相对降低,差异有统计学意义（P＜0.05）;术后第10天,BG100组[（5.35±0.85）g]和BG200组[（5.71±0.72）g]与BN组[（2.61±0.40）g]和BG50组[（3.28±1.15）g]比较,MWT明显升高,差异有统计学意义（P＜0.05）;直到术后14d,差异仍有统计学意义（P＜0.05）;从术后第8天起,BG100组和BG200组自由行走痛行为评分较BN组降低,差异有统计学意义（P＜0.05）.结论 中到大剂量的加巴喷丁可以缓解骨癌痛大鼠的疼痛症状,但是随着肿瘤骨破坏的加重,加巴喷丁的止痛作用也随之降低.

Objective To explore the effects of gabapentin on mechanical allodynia in rats with tibial bone cancer pain （BCP）.Methods Forty-two female SD rats were randomized into 7 groups （ n=6）：naive group （group N ）,sham operation ＋ NS control group （group SN）,sham operation ＋ GBP200mg/（ kg · d） group （group SG200）,BCP ＋ NS control group （group BN）,BCP ＋ GBP50mg/（ kg · d） group （ group BGS0）,BCP ＋GBP100mg/（kg · d） group （group BG100）,and BCP ＋ GBP200mg/（kg · d） group （group BG200）.The rats in group N,SN and BN received 5 ml normal saline and the rats in group SG200,BG50,BG100 and BG200 received 200,50,100 and 200 mg/（ kg · d） dose of GBP via feeding from day 7 to 13 after operation,respectively.Mechanical withdrawal threshold（MWT） of the right paw and behavioral assays for ambulatory pain were measured just before operation and on days 1,3,5,7,8,10,12 and 14 after operation.Results MWT（ （3.78 ± 0.38）g） in rats with BCP decreased and behavioral assays for ambulatory pain （0.76 ± 0.44） increased on day 7 after operation,as compared with those in group N （ （ 14.50 ± 1.38 ） g,（0.00 ± 0.00 ） ） and group sham （ （ 10.21 ± 0.88 ） g,（ 0.00 ±0.00） ） （P 〈 0.05 ）.There was no apparent praxiological difference between group SN and group SG200 in a week of continuous application of gabapentin（P〉 0.05 ）.Compared with those in group BN,there was no change on MWT in group BG50 （P 〉 0.05 ）,and however,behavioral assays for ambulatory pain decreased （P 〈 0.05 ）.MWT in group BG100（ （5.35 ±0.85）g） and BG200（ （5.71 ±0.72） g） increased in day 10 after operation,as compared with those in group BN （ （ 2.61 ± 0.40） g） and group BG50 （ （ 3.28 ± 1.15 ） g） （P 〈 0.05 ）,and the difference was still statistically significant until day 14 （P 〈 0.05 ）.Behavioral assays for ambulatory pain in group BG100 and BG200 decreased from day 8 after operation,as compared with those in group BN and group BG50 （P 〈 0.05 ）.Conclusion Gabapentin,in medium to large dosage,can inhibit pain reaction of rats with bone cancer pain.Nevertheless,with the development of cancer,the effect of gabapentin decreases.