国际麻醉学与复苏杂志   2015, Issue (1): 9-9
    
加巴喷丁对骨癌痛大鼠脊髓CX3CR1受体表达的影响
范钦, 李晶, 程伟, 殷琴, 闫长栋1()
1.徐州医学院
Effects of gabapentin on the expression of spinal CX3CR1 receptor in a rat model of bone cancer pain
 全文:
摘要:

目的 观察加巴喷丁(gabapentin, GBP)对骨癌痛(bone cancer pain, BCP)大鼠脊髓CX3CR1受体表达的影响。 方法 雌性Sprague-Dawley(SD)大鼠40只,采用随机数字表法将其随机分为5组(每组8只):正常对照组(N组)、假手术组(右侧胫骨骨髓腔内注入生理盐水)(SN组)、BCP组、BCP+生理盐水组(BN组)、BCP+GBP 200 mg·kg-1·d-1组(BG 200组)。术后7 d~14 d,GBP 200 mg·kg-1·d-1溶于5 ml生理盐水中饲喂BG 200组大鼠,SN组、BN组喂食等容积的生理盐水。分别于术前1 d(T0)及术后1(T1)、3(T2)、5(T3)、7(T4)、9(T5)、11(T6)、14 d(T7)测定大鼠50%的机械缩足反射阈值(paw withdrawal mechanical threshold, PWMT)及自发性疼痛评分(behavioral assays for ambulatory pain, BAAP),Western blot法测定脊髓CX3CR1蛋白的表达水平。 结果 与N组[(13.2±1.0) g ]比较,术后第3天开始,BCP组大鼠PWMT[(10.5±0.4) g]减少;与N组(0分)比较,术后第5天BCP组BAAP[(2.0±0.8) 分]增加。与BN组[(3.0±0.8) g]比较,术后第9天BG 200组大鼠PWMT[(6.1±0.9) g]增加;与BN组[(2.8±0.5) 分]比较,术后第9天BG 200组大鼠BAAP[(1.6±0.7) 分]减少;一直持续到第14天,差异仍有统计学意义(P<0.01)。与N组比较,术后第3天开始,BCP组大鼠脊髓CX3CR1表达增加。与BN组比较,BG 200组大鼠脊髓CX3CR1表达下调(P<0.01)。 结论 GBP可以减轻BCP大鼠的痛觉过敏,其机制可能与降低脊髓CX3CR1表达有关。

关键词: 加巴喷丁; CX3CR1; 骨癌痛; 机械缩足反射阈值; 自发性疼痛评分
Abstract:

Objective To explore the effects of administration of gabapentin on the expression of spinal CX3CR1 receptor in rats with tibial bone cancer pain(BCP). Methods Forty female Sprague-Dawley(SD) rats were randomized into 5 groups(n=8): naive group(group N), sham operation+NS control group(group SN), BCP group, BCP+NS control group (group BN), and BCP+GBP 200 mg·kg-1·d-1 group(group BG 200). The rats in group SN and BN received 5 ml normal saline and the rats in group BG 200 received 5 ml 200 mg·kg-1·d-1 dose of GBP via feeding from day 7 to 14 after operation, respectively. Fifty percent of paw withdrawal mechanical threshold(PWMT) of the right paw and behavioral assays for ambulatory pain(BAAP) were measured just 1 d(T0) before operation and on days 1(T1),3(T2),5(T3),7(T4),9(T5),11(T6) and 14(T7) after operation; Western blot assay of CX3CR1 protein expression levels of the spinal cord were carried out. Results PWMT(10.5±0.4) g in rats with BCP decreased on day 3 after operation, and BAAP(2.0±0.8) increased on day 5 after operation, as compared with those in group N[(13.2±1.0) g, 0]. PWMT(6.1±0.9) g in BG 200 increased and BAAP(1.6±0.7) decreased on day 9 after operation, as compared with those in group BN[(3.0±0.8) g,(2.8±0.5)], and the difference was still statistically significant until day 14(P<0.01). The expression of spinal CX3CR1 increased from day 3 after operation in a rat model of bone cancer pain,as compared with those in group N. The expression of spinal CX3CR1 in group BG 200 decreased as compared with those in group BN(P<0.01). Conclusions Gabapentin attenuates the hyperalgesia in rats of of bone cancer pain, which may be associated with decreased spinal CX3CR1.

Key words: Gabapentin; CX3CR1; Bone cancer pain; Paw withdrawal mechanical threshold; Behavioral assays for ambulatory pain