[目的]观察Walker256乳腺癌细胞所致骨癌痛吗啡耐受大鼠的模型特点及不同时间介入电针治疗对骨癌痛吗啡耐受大鼠的疗效。[方法]清洁级健康雌性SD大鼠53只,随机分为6组:假手术组(Sham)、骨癌痛组(BCP)、骨癌痛-吗啡耐受组(MT)、电针Ⅰ组(EA I)、电针Ⅱ组(EA II)、假电针组(Sham EA)。除sham组外,将10μL Walker256乳腺癌细胞(1×105cell)注入各组大鼠左侧胫骨髓腔内,于术后7d,将MT组、EAⅠ组、EAⅡ组、sham EA组骨癌痛制备成功的大鼠行腹腔注射盐酸吗啡(10mg·kg^-1,2次/d)连续11d,诱导骨癌痛-吗啡耐受模型。EA I组于吗啡耐受前(即术后7d)介入电针干预,采用2/100Hz电针,刺激双侧"足三里"和"昆仑"穴,连续刺激18d;EA II组于吗啡耐受后第1d(即术后18d)介入电针治疗,方法同EAⅠ组,连续治疗7d;Sham EA组大鼠仅给予针刺破皮,不予通电治疗,其穴位及治疗时间同EA II组。观察大鼠患侧机械缩足阈(paw withdrawal thresholds,PWT)评价电针治疗效果。[结果]癌细胞接种后第6d(即术后6d),BCP组和MT组大鼠患侧PWT均明显低于Sham组大鼠(P〈0.01)。吗啡注射第1d,MT组大鼠患侧PWT显著高于BCP组大鼠(P〈0.01);吗啡连续注射11d(术后17d)后MT组大鼠PWT下降至BCP组大鼠同等水平(P〉0.05)。吗啡耐受前介入电针干预后第9d-13d(即术后第15d-19d),EA I组大鼠PWT明显高于MT组大鼠(P〈0.05或P〈0.01);而术后第20d至24d,EA I组大鼠PWT与MT组比较无统计学差异(P〉0.05)。吗啡耐受后介入电针治疗第1d-7d,EA II组大鼠患侧PWT较MT组和Sham EA组均明显升高(P〈0.05或P〈0.01)。[结论]骨癌痛大鼠给予腹腔连续注射吗啡11d时,即可成功诱导癌痛大鼠吗啡耐受模型;吗啡耐受前给予电针预刺激可延缓骨癌痛大鼠吗啡耐受产生;吗啡耐受后给予电针治疗可部分翻转骨癌痛大鼠吗啡耐受效应。
[Objective]Investigating the characteristic of morphine tolerance model in rats with bone cancer pain induced by Walker 256 breast cancer cell and observating the therapeutic effect of electroacupuncture(EA) at different time on morphine tolerance. [Methods]The 53 SD rats were randomly divided into 6groups: sham group(Sham), bone cancer pain group(BCP), bone cancer pain+morphine tolerance group(MT),EA I group(EA Ⅰ), EA II group(EAⅡ), Sham EA group(Sham EA). The 10μL Walker 256 breast cancer cells(1 ×105) were injected into left tibial bone marrow cavity of rat. At 7 days after surgery, the successful preparation of bone cancer pain in rats by intraperitoneal injecting morphine hydrochloride continuous 11d(10mg·kg^-1, q12h) to induce morphine tolerance. Before morphine tolerance(Seventh day after operation), rats in EA I group were treated with electroacupuncture, which had been lasted for 18 days. The first day after morphine tolerance, rats in EA II group were involved in EA treatment, continuing for 7 days. EA was applied to bilateral"Zusanli"(ST36) and "Kunlun"(BL60). Rats in Sham EA group were only given acupuncture to break the skin, and no electricity,the acupoint and treatment time were consistent with EA II group. Observing the changes of PWT to evaluate the effect of EA. [Results]After 6 days of the cancer cells were inoculated, the PWT of the BCP group and MT group was significantly lower than that of the Sham group(P〈0.01). The first day after morphine injection, the PWT of MT group was significantly higher than those of the BCP group(P〈0.01). With morphine for 11 consecutive days(17 days after operation), the PWT of MT group was decreased to the same level of the BCP group(P〉0.05). At 9d to 13 d after EA intervention, the PWT of EA I group was significantly higher than those of MT group(P〈0.05 or P〈0.01), before the morphine tolerance established. To 20 days after operation, there was no significant differ