前列腺酸性磷酸酶参与骨癌痛大鼠脊髓镇痛的行为学研究

A behavior study on prostatic acid phosphatase involved in spinal analgesia in rat models of cancer-induced bone pain

目的:运用行为药理学方法,观察前列腺酸性磷酸酶(prostatic acid phosphatase,PAP)在骨癌痛(cancer-induced bone pain,CIBP)大鼠脊髓的镇痛效应。方法:本研究用SD雌性大鼠30只,随机分为5组(n=6):假手术+生理盐水(Ⅰ组)、假手术+hPAP(Ⅱ组)、模型+生理盐水(Ⅲ组)和模型+hPAP(Ⅳ组)、空白对照组(Ⅴ组)。麻醉后,Ⅰ组和Ⅱ组右侧胫骨骨髓腔内注入5μl生理盐水;Ⅲ组和Ⅳ组于右侧胫骨骨髓腔内接种5μl大鼠乳腺癌细胞(2×105个),14d后造模完成。接种后第15天Ⅰ、Ⅲ组鞘内分别给予5μl生理盐水,Ⅱ、Ⅳ组鞘内分别给予5μl hPAP(1U),接种后第17天,Ⅳ组腹腔注射选择性腺苷A1受体拮抗剂8-环戊基1,3-二丙基黄嘌呤(8-cyclopentyl-1,3-dipropylxanthine,CPX)。于接种前、接种后第3、6、9、12、15、16、17、18、19、20和21天分别测量大鼠的机械性和热刺激的缩足阈值。结果:PAP对骨癌痛模型大鼠具有良好的镇痛效果,且镇痛效应能维持3d左右,未观察到运动阻碍、成瘾及耐受等不良反应;CPX可以基本翻转PAP在脊髓水平对痛觉传递的抑制作用。结论:PAP可能成为一个新的治疗癌性痛的潜在药物分子。

Objective:To observe the spinal analgesic effect of prostatic acid phosphatase(PAP)in the rat models of cancer-induced bone pain by behavioral pharmacology method.Methods:Twenty-four adult female Sprague-Dawley rats were randomly divided into 4groups(6rats in each group),including groupⅠ(sham-operation + normal saline),group Ⅱ(sham-operation + hPAP),group Ⅲ(tumor cell inoculation + normal saline),group Ⅳ(tumor cell inoculation + hPAP)and group Ⅴ(naive).After anesthesia,5μl of normal saline(NS)were injected into marrow cavities of right tibial bones of rats in groupⅠ andⅢ while 5μl of mammary gland carcinoma cells culture(2×105)were inoculated into marrow cavities of right tibial bones of rats in groupⅡ and Ⅳ.The model of bone cancer pain was made 14 days later.On the 15 th day after inoculation,5μl of NS were given intrathecally to rats of groupⅠ andⅢ while5μl hPAP(1 U)were given intrathecally in rats of group Ⅱ and Ⅳ.On the 17 th day of inoculation,the selective A1 Rantagonist 8-cyclopentyl-1,3-dipropylxanthine(CPX)was injected intraperitoneally in rats of group Ⅳ.Shrinkage thresholds upon mechanical and thermal stimulation were measured 3,6,9,12,15,16,17,18,19,20,21 days after and before inoculation.Results:PAP showed a good analgesic effect on rats of cancer-induced bone pain models.The effect continued for three days.No adverse reactions such as movement obstruction,addiction and tolerance were observed.CPX could reverse the inhibitory effect of PAP on pain transmission in the spinal cord level.Conclusion:PAP may be a new potential medicine in the treatment of cancer pain.