| Part I: the clinical research on the traditional Chinese plaster of Ailitong to treat the moderate to severe pain caused by osseous metastasis tumor ObjectiveTaking the patients suffering from moderate to severe pain caused by osseous metastasis tumor as the subjects investigated,evaluation on the therapeutic effect and security of the traditional Chinese plaster of Ailitong.To observe the level of serous NGF?TNF-??ET-1??-EP,elucidate the mechanism of external application of the plaster of Ailitong.MethodsUsing the clinical stratified randomized controlled methods,90 cases of moderate to severe pain caused by osseous metastasis tumor were randomly divided into treatment and control groups,each group contains 45 patients.The control group received pure oral administration Oxycodone.The treatment group on the basis of oral Oxycodone,with traditional Chinese plaster of Ailitong.The key indicators in respect to the scores of pain influence,quality of life(Karnofsky performance score),pain score(NRS performance score),the dosage of Oxycodone,burst pain condition and the level of serous NGF?TNF-??ET-1??-EP were compared between the groups before and after treatment;and the therapeutic action of differential treatment by plaster of Ailitong on the pain caused by osseous metastasis tumor were comprehensively analyzed,scientifically evaluated and observed.Results1.The baseline situation:A baseline analysis was conducted on the ages of all the cases in the groups as well as the proportion of men to women in the groups to find out a proportion of 46.7% and 57.8% between male patients and female patients in the treatment group,and a proportion of 42.2% and 57.8% between male patients and female patients in control group and ?2 test results indicated no significant difference statistically in the proportion of male-female in the two groups(P>0.05).The ages between the treatment group and the control group were respectively 57.64±13.62 and 59.16±12.69,and the t test results indicated no significant difference statistically in the ages of the two groups(P>0.05).The proportion of disease in the groups to find out a proportion of 37.7% and 63.5% between osteosarcoma patients and patients with bone metastases.There were 15 cases of moderate bone pain and 30 cases of severe bone pain in the treatment group,19 cases of moderate bone pain and 26 cases of severe bone pain in the control group,no significant difference statistically in the pain degree of the two groups.2.Therapeutic effect2.1 Patients with moderate bone pain2.1.1 Pain scores:In terms of comparison of NRS score between two groups before treatment,the treatment group was 4.93±0.80 while that of the control group was 4.79±0.79 with no significant difference in statistic(P>0.05),indicating that the two groups were comparable;NRS score between two groups after treatment was significantly decreased,the treatment group was 1.80±0.94 while the control group was 1.74±0.96(P<0.05).The comparison between two groups after treatment had no significant difference(P>0.05).2.1.2 Effectiveness ratio of scores of pain:After 10 days of treatment,there were 2 cases complete remissions,10 cases of obvious remissions and 3 cases of slight remissions in treatment group in terms of scores of pain with a effective rate of 80% while 3 cases complete remissions,15 cases of obvious remissions and 1 case of slight remissions in control group with a effective rate of 94.74%.There was no significant difference statistically in the effectiveness ratio of scores of pain in the two groups after treatment(P>0.05).2.1.3 Dosage of Oxycodone:Single dosage of Oxycodone on the first day of two groups before treatment were 10 mg per time,oral once every 12 h.After treatment,the single dosage of Oxycodone of the treatment group was(12.67±5.94)mg with no significant difference in statistic(P>0.05)compared with that before treatment,while the single dosage of Oxycodone of the control group was(21.58±8.34)mg with a significant difference in statistic(P<0.05) compared with that before treatment;the comparison between two groups after treatment had a significant difference(P<0.05).2.1.4 Burst pain condition: There were(0.40±0.51)times burst pain in the treatment group and(0.63±0.49)times in the control group,no significant difference statistically in the times of burst pain in the two groups(P>0.05).2.1.5 Evaluation of QOL:In terms of comparison of KPS score between two groups before treatment,the treatment group was 67.33±17.51 while that of the control group was 65.26±18.67 with no significant difference in statistic(P>0.05),indicating that the two groups were comparable.KPS score between two groups after treatment in the treatment group was 70.00±15.58 while the control group was 67.89±15.12.There were no significant difference in the same group and with the other group(P>0.05).2.1.6 Levels of related markers of pain:In terms of comparison of serous NGF concentration between two groups before treatment,the treatment group was(35.34 ± 74.79)pg/m L while that of the control group was(21.89 ±66.64)pg/m L with no significant difference in statistic(P>0.05),indicating that the two groups were comparable.The serous NGF concentration between two groups after treatment in the treatment group was(25.39±58.55)pg/m L while the control group was(34.8±66.82)pg/m L..The serous NGF concentration in the treatment group was significantly lower than that in the control group(P<0.05).In terms of comparison of serous TNF-? concentration between two groups before treatment,the treatment group was(9.67±8.35)ng/m L while that of the control group was(10.48±5.33)ng/m L with no significant difference in statistic(P>0.05),indicating that the two groups were comparable.The serous TNF-? concentration between two groups after treatment in the treatment group was(3.83±2.28)ng/m L while the control group was(24.90±18.84)ng/m L..The serous TNF-? concentration in the treatment group was significantly lower than that in the control group(P<0.05).In terms of comparison of serous ET-1 concentration between two groups before treatment,the treatment group was(1.68±2.45)pg/m L while that of the control group was(6.29±11.84)pg/m L with no significant difference in statistic(P>0.05),indicating that the two groups were comparable.The serous ET-1 concentration between two groups after treatment in the treatment group was(0.81±0.98)pg/m L while the control group was(17.01±22.54)pg/m L..The serous ET-1 concentration in the treatment group was significantly lower than that in the control group(P<0.05).In terms of comparison of serous?-EP concentration between two groups before treatment,the treatment group was(43.20±106.76)ng/m L while that of the control group was(67.00±93.51)ng/m L with no significant difference in statistic(P>0.05),indicating that the two groups were comparable.The serous?-EP concentration between two groups after treatment in the treatment group was(30.84±54.44)ng/m L while the control group was(64.92±78.86)ng/m L.The serous ?-EP concentration of two groups after treatment was slightly decreased,but there had no significant difference in statistic compared before treatment(P>0.05).2.2 Patients with severe bone pain2.2.1 Pain scores:In terms of comparison of NRS score between two groups before treatment,the treatment group was 8.07±0.98 while that of the control group was 8.12±0.95 with no significant difference in statistic(P>0.05),indicating that the two groups were comparable;NRS score between two groups after treatment was significantly decreased,the treatment group was 3.10±2.26 while the control group was 4.85±2.13(P<0.05).The NRS score in the treatment group was significantly lower than that in the control group after treatment(P<0.05).2.2.2 Effectiveness ratio of scores of pain:After 10 days of treatment,there were 1 case complete remissions,24 cases of obvious remissions and 1 case of slight remissions in treatment group in terms of scores of pain with a effective rate of 83.33% while 13 cases of obvious remissions and 7 case of slight remissions in control group with a effective rate of 50%.There was a significant difference statistically in the effectiveness ratio of scores of pain in the two groups after treatment(P<0.05).2.2.3 Dosage of Oxycodone:Single dosage of Oxycodone on the first day of two groups before treatment were 20 mg per time,oral once every 12 h.After treatment,the single dosage of Oxycodone of the treatment group was(26.67±8.44)mg with significant difference in statistic(P<0.05)compared with that before treatment,while the single dosage of Oxycodone of the control group was(33.46±7.97)mg with a significant difference in statistic(P<0.05)compared with that before treatment;the comparison between two groups after treatment had a significant difference(P<0.05).2.2.4 Burst pain condition: There were(0.90±1.03)times burst painin the treatment group and(1.81±0.85)times in the control group,there was a significant difference statistically in the times of burst pain in the two groups(P<0.05).2.2.5 Evaluation of QOL:In terms of comparison of KPS score between two groups before treatment,the treatment group was 40.00±14.86 while that of the control group was 37.31±13.13 with no significant difference in statistic(P>0.05),indicating that the two groups were comparable.KPS score between two groups after treatment was significantly improved,the treatment group was 52.67±13.11 while the control group was 44.23±14.19(P<0.05).The KPS score in the treatment group was significantly higher than that in the control group after treatment(P<0.05).2.2.6 Levels of related markers of pain:In terms of comparison of serous NGF concentration between two groups before treatment,the treatment group was(18.24±42.25)pg/m L while that of the control group was(32.38±85.60)pg/m L with no significant difference in statistic(P>0.05),indicating that the two groups were comparable.The serous NGF concentration between two groups after treatment in the treatment group was(8.92±18.62)pg/m L while the control group was(54.43±109.95)pg/m L.The serous NGF concentration in the treatment group was significantly lower than that in the control group(P<0.05).In terms of comparison of serous TNF-? concentration between two groups before treatment,the treatment group was(24.74±66.72)ng/m L while that of the control group was(10.23±7.99)ng/m L with no significant difference in statistic(P>0.05),indicating that the two groups were comparable.The serous TNF-? concentration between two groups after treatment in the treatment group was(14.02±37.66)ng/m L while the control group was(19.58±15.94)ng/m L..The serous TNF-? concentration in the treatment group was significantly lower than that in the control group(P<0.05).In terms of comparison of serous ET-1 concentration between two groups before treatment,the treatment group was(8.53±12.49)pg/m L while that of the control group was(4.95±11.16)pg/m L with no significant difference in statistic(P>0.05),indicating that the two groups were comparable.The serous ET-1 concentration between two groups after treatment in the treatment group was(4.29±7.33)pg/m L while the control group was(12.63±18.61)pg/m L..The serous ET-1 concentration in the treatment group was significantly lower than that in the control group(P<0.05).In terms of comparison of serous?-EP concentration between two groups before treatment,the treatment group was(128.47±168.21)ng/m L while that of the control group was(91.90±149.58)ng/m L with no significant difference in statistic(P>0.05),indicating that the two groups were comparable.The serous?-EP concentration between two groups after treatment in the treatment group was(137.07±168.12)ng/m L while the control group was(81.14±121.60)ng/m L.The serous ?-EP concentration in the treatment group was significantly higher than that in the control group(P<0.05).3.Safety evaluation: The adverse reactions of the two groups were mainly caused by opioid drugs,which caused nausea,constipation and headache.In the treatment group,there were 2 cases of mild skin itching,which were better after treatment,indicating the traditional Chinese plaster of Ailitong was safe in use without remarkable adverse effect or toxic effect.Conclusion1.For patients with moderate cancer-related bone pain,on the basis of Oxycodone,the use of traditional Chinese plaster of Ailitong can reduce the dosage of painkillers,but there were no significant difference statistically in the pain scores?effectiveness ratio of scores of pain?times of burst pain and KPS scores(P>0.05).2.For patients with severe cancer-related bone pain,on the basis of Oxycodone,the use of traditional Chinese plaster of Ailitong can reduce the dosage of painkillers,improve the effectiveness ratio of scores of pain,reduce times of burst pain and improve patients' quality of life(P<0.05).There is more advantage in the Ailitong treatment of patients with severe cancer-related bone pain.so we can use it more in the future.3.As the NRS scores were significantly decreased for patients with moderate or severe pain in two groups,but the changing trends of the levels of NGF?TNF-??ET-1??-EP in treatment group were all opposite to that of in control group.In addition,the original data of NGF,TNF-alpha,beta-EP concentration difference is large,resulting in large standard deviation statistics,this may result in the test between the different primary disease and fewer samples included in this study.This study confirmed that Ailitong have definite effects in the patients,and corresponding effects for NGF?TNF-??ET-1??-EP.But this study does not figure out the relationship between the concentration of NGF?TNF-??ET-1??-EP and pain management.4.The traditional Chinese plaster of Ailitong was safe in use without remarkable adverse effect or toxic effect.5.Ailitong has good curative effect,but failed to make it clear the relationship between pain factor and pain control.So we designed the animal experiments,which proved the ailitong efficacy and explored the mechanism of analgesia.Part II: the experimental research on the traditional Chinese plaster of Ailitong to treat cancer-related painObjectiveThe Walker 256 breast cancer cells were inoculated into the nude mice.Tumors were established by the injection of Walker 256 breast cancer cells,the nude mice received external application of plaster of Ailitong.Then we evaluated it's analgesic effect.So as to verify whether the traditional Chinese plaster of Ailitong have a analgesic effect for cancer pain,we test the level of serous NGF?TNF-??ET-1??-EP and explore the analgesic mechanism.MethodsTumors were established by the injection of Walker 256 breast cancer cells,the 16 mice were randomly divided into 2 groups of 8 each experiment:(1)Control group:0.9% Na Cl;(2)Ailitong group: plaster of Ailitong 61g/kg for 10 days,six hours a day.Spontaneous pain score were assessed at 1,3,5,7,10 d after administration,the tumor diameter were measured twice a week,tumor weight were measured after research.Finally the spinal cords were removed for Q-PCR to quantify the level of NGF?TNF-??ET-1??-EP.Results1.The rat body weight change: There were no significant differences statistically in the rat body weight change for the two groups compare with pre-experiment at various time points(P>0.05).The comparison between two groups after treatment had no significant difference at various time points(P>0.05).2.Spontaneous pain scores: spontaneous pain score between two groups after model establishment was increased with observation time,the score of Ailitong group was significantly lower than the control group at d3,d10(P<0.05).3.Tumor volume and tumor proliferative rate: There was no significant difference statistically in the tumor volume for the two groups,indicating that the two groups were comparable.Tumor volume and relative tumor volume between two groups after model establishment were all increased with observation time.The tumor volume and relative tumor volume of Ailitong group were significantly lower than the control group at d3,d7,d10(P<0.05).Tumor proliferative rate was 39.7% in the Ailitong group after treatment.4.Tumor weight: The tumor weight of Ailitong group were significantly lower than the control group(P<0.05),tumor inhibition rate was 39.7% in the Ailitong group after treatment.5.Levels of related markers of pain: The spinal cords were removed for Q-PCR to quantify the level of NGF?TNF-??ET-1??-EP,the comparison between two groups after treatment had no significant difference(P>0.05).Conclusion1.A skin cancer pain model of Walker 256 breast cancer cells in nude mice is successfully established;2.The use of traditional Chinese plaster of Ailitong can improve the spontaneous pain caused by tumor of Walker 256 breast cancer cells in nude mice;3.The use of traditional Chinese plaster of Ailitong can inhibit tumor growth of Walker 256 breast cancer cells in nude mice;4.This study does not figure out the relationship between the concentration of NGF?TNF-??ET-1??-EP and spontaneous pain caused by tumor of Walker 256 breast cancer cells in nude mice. |
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