镇痛膏外用缓解癌性疼痛的作用及相关机制研究

目的：利用癌痛动物模型研究镇痛膏缓解癌性疼痛的作用及其作用机制。方法：建立小鼠肺癌股骨癌痛模型,实验分镇痛膏组、硫酸四氢帕马丁组、生理盐水组和假手术组。从造模第10天给药,连用5d。镇痛膏组,10g/kg;生理盐水组和假手术组,0.5ml/只;硫酸四氢帕马丁组在造模第14天,单次6.498mg/kg肌注。在末次给药后测量各组小鼠的痛行为,包括机械性痛觉超敏和热刺激痛觉过敏;将小鼠股骨进行X线摄片,影像学评估骨破坏;并用免疫组化法检测各组局灶皮肤组织TNFα、ET-1、IL-1β水平及脊髓后角SP-R、c-fos及GFAP阳性反应神经元的表达。结果：造模第14天,镇痛膏组、硫酸四氢帕马丁组、生理盐水组小鼠对2gVonFrey纤维刺激的缩足反应百分率分别为12.5%±14.88%、26.67%±16.33%、60%±28.28%,与生理盐水组比较,镇痛膏组缩足反应百分率明显下降（P〈0.01）;热刺激痛阈时间镇痛膏组、硫酸四氢帕马丁组、生理盐水组小鼠分别为（17.58±4.16）s、（16.50±2.76）s、（11.96±2.01）s,与生理盐水组比较,镇痛膏组热刺激痛阈升高（P〈0.01）。同时股骨X线显示,镇痛膏组骨破坏程度较轻,放射学评分下降;镇痛膏组局灶皮肤组织TNFα、ET-1、IL-1β水平及脊髓后角SP-R、c-fos及GFAP阳性反应神经元表达均明显减少。结论：镇痛膏对癌痛小鼠治疗有效,能够减轻痛行为,延缓骨破坏,其镇痛机制可能与外周和中枢机制共同参与有关。

Study on the Effect of Zhentong Plaster in External Use on the Alleviation of Cancer Pain and Its Mechanism

Objective：To study the effect of Zhentong plaster on the alleviation of cancer pain and its mechanism in the mice of cancerous pain.Methods：The mice were induced to osseous metastases of lung cancer.Then they were divided into Zhentong plaster group,Tetrahydropalmatine Sulfate group,normal saline group and sham-operation group.The mice in Zhentong plaster group had been administrated with Zhentong plaster（10 g/kg） for five days on the 10th day after inducing the mice to osseous metastases of lung cancer;The mice in normal saline group and sham-operation group had been administrated with normal saline（0.5 ml/mouse） for five days on the 10th day after inducing the mice to osseous metastases of lung cancer;The mice in Tetrahydropalmatine Sulfate group had been administrated with Tetrahydropalmatine Sulfate（6.498 mg/kg） for five days on the 14th day after inducing the mice to osseous metastases of lung cancer.After the last administration of the mice,the activities of mice mediated by cancer pain were detected,including mechanical allodynia and thermal hyperalgesia;The thighbones of mice were examined and evaluated by X-ray.In addition,the expressions of TNFα、ET-1、IL-1β in special skin tissues;SP-R、c-fos in dorsal horn of spinal cord and GFAP in positie neurons were detected with the method of Immunohistochemistry.Results：The paw withdrawal percentages of mice stimulated by 2 g Von Frey fibre in Zhentong plaster group,Tetrahydropalmatine Sulfate group and normal saline group were 12.5% ± 14.88%,26.67% ± 16.33%,60% ± 28.28% separately and the paw withdrawal percentages in Zhentong plaster group were decreased obviously（P 〈0.01） compared with that in normal saline group;the duration of pain threshold mediated by thermal hyperalgesia in the mice of Zhentong plaster group,Tetrahydropalmatine Sulfate group and normal saline group were（17.58 ± 4.16） s,（16.50 ± 2.76） s,（11.96 ± 2.01） s separately and the duration of pain threshold in the Zhentong plaster group was longer（P〈 0.01） than that in normal saline group.In addition,the X-ray in the thighbones of the mice indicated that the degree of bone destruction in Zhentong plaster group was slight,radiology score was decreased and the expressions of TNFα、ET-1、IL-1β in special skin tissues;SP-R、c-fos in dorsal horn of spinal cord and GFAP in positie neurons were decreased obviously.Conclusion：the Zhentong plaster can improve the treatment of cancer pain in the mice of osseous metastases of lung cancer,alleviate the pain activities and retard the bone destruction in mice.Its mechanism may be related to the functions of both peripheral nervous system and central nervous system.