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+GBP200mg·kg^-1·d^-1组(BG200组)。术后7d-14d,GBP200mg·kg^-1·d^-1溶于5m性理盐水中饲喂BG200组大鼠,SN组、BN组喂食等容积的生理盐水。分别于术前1d(T0)及术后1(T1)、3(T2)、5(T3)、7(T4)、9(T5)、11(T6)、14d(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BG200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BG200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,BG200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。
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^-1dose 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 (TO) before operation and on days 1(T1),3(T2),5(T3),7(T4),9(TS),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.