| Cancer pain is one of the most common symptoms in patients with advanced cancer.Cancer Pain can reduce the quality of life of patients with cancer,and even shorten the survival of patients with cancer.At present,the clinical methods of controlling/treatment of cancer pain mainly includes drug treatment and non-drug treatment,but there are still problems of insufficient analgesic effect and side effects of drugs.Use low-frequency and low-power ultrasound as an intervention method to radiation the animal models with cancer pain and clinical cancer pain patients,and to exploring the effectiveness of ultrasonic radiation in relieving cancer pain,in order to provide a treatment which is safe,non-invasive,simple and effective for relieving cancer pain of the patients.It mainly includes the following contents:1.Walker256 cells were injected into rat tibia.Rat behavioral,hematoxylin-eosin staining,imaging,biochemical indicators related with bone cancer were used as evaluation criteria to comprehensively evaluate model rats.Finally complete the model building;2.Observing and recording the behavioral changes of experimental animals and detecting related biochemical indicators after the rats with bone cancer pain were radiated by ultrasound,analyze the possible causes of ultrasound to alleviate cancer pain,and evaluate the effectiveness of ultrasound to alleviate cancer pain,and provide feasible basis for clinical trials;3.Based on the ultrasound to effectively alleviate the symptoms of cancer pain in the model rat,conduct clinical trial research.Patients with cancer pain who met the inclusion criteria were randomly divided into treatment group and control group.After treatment,the two groups were compared with cancer pain impact score,analgesic drug use,NRS score and pain relief rate to evaluate the effect of ultrasound radiation to alleviate cancer pain.Method1.Method for establishing bone cancer pain modelWalker 256 cells were inoculated into the peritoneal cavity of the rat for proliferation,and the proliferated cells were taken out and directly injected into the left tibia of the rat to complete the modeling operation.Spontaneous ambulatory pain score and mechanical paw withdrawal thresholds were measured in the model group on days 0,4,6,8,10,12,and 14 of the surgery.On the 14 th day of modeling,the tibia of the model group was examined by imaging and HE staining.The contents of TNF-?,IL-1? and IL-6 in serum and the expression levels of astrocyte marker protein GFAP and microglia marker protein IBA-1 in the spinal cord were detected.Based on the above indicators,the model was comprehensively evaluated and a control group was established.2.Experimental study method of ultrasonic radiation to alleviate bone cancer pain animal model2.1 Grouping of experimental animals2.1.1 Model observation group: BCP1 d,BCP5d,BCP10 d,respectively,indicating that the model was successfully established(14 days after modeling),and the rats were randomly divided into 1 day group,5 day group,and 10 day group(ie,15 days,19 days and 24 days after modeling).2.1.2 Ultrasound radiation group: Rats with successful modeling were randomly divided into US1~US9 groups(Table 1).2.1.3 Blank control group: rats that were not modeled and did not undergo any treatment2.2 The model rats(divided into US1~US9 groups,Table 1)was irradiated by ultrasound(f=20 k Hz,P=0.3 W/cm2).After irradiation,the spontaneous ambulatory pain score,mechanical paw withdrawal thresholds,the levels of TNF-?,IL-1? and IL-6 and expression of GFAP and IBA-1 marker proteins in the spinal cord were measured.3.Clinical trial methods for ultrasonic radiation to alleviate cancer PainAccording to the exclusion criteria,106 patients with cancer pain were enrolled.The patients with cancer pain were divided into a treatment group of 51 cases and a control group of 55 cases.The control group received conventional drug therapy with placebo ultrasound radiation.The treatment group was given conventional medical treatment with ultrasound radiation therapy.At the end of the course of treatment(14 days),the clinical efficacy of ultrasound to alleviate cancer pain was comprehensively evaluated by comparing the pain intensity score,pain impact assessment,analgesic drug use dose,and cancer pain relief rate index between the two groups.Result1.Establishment of bone cancer pain model1.1 On the 6th day after model establishment,the spontaneous ambulatory pain scores of the model group were statistically different from the control group(P<0.01).With the increase of time,the pain scores of the model group gradually increased;on the 8th day after modeling,the mechanical paw withdrawal thresholds in the model group was significantly lower than that in the control group(P<0.01),followed by a progressive decline.1.2 On the 14 th day of modeling,the results of tibial imaging test and HE staining showed that the bone destruction,bone density decreased,density was uneven,and a large number of tumor cells in the bone marrow cavity were observed in model group.And the IOD values of astrocyte markers GFAP and microglia IBA-1 in the spinal cord of the model group with altered behavior were statistically different from those in the control group(P<0.01);There were also statistical differences between serum TNF-?,IL-1?,IL-6 levels and control group(P<0.01).2.Experimental results of animal models of bone cancer pain relieved by ultrasonic radiation2.1 In the US group,with the prolongation of the time and the number of days of ultrasound radiation,the overall pain score of rats showed a downward trend,and the mechanical paw withdrawal thresholds increased gradually.There were statistical differences between the US4~US6 group and BCP5 d group,US7~US9 group and BCP10 d group in pain score and mechanical paw withdrawal thresholds(P<0.01).Among them,the US9 group's pain score and mechanical paw withdrawal thresholds were not different from the control group(P>0.05).2.2 In the US group,there was no difference in the IOD values of the two cell marker proteins in the spinal cord of the US1~US3 group and the BCP1 d group(P>0.05).The IOD values of the other groups of the marker proteins were statistically significant compared with the model observation groups at the corresponding time(P<0.05).Among them,the IOD value of GFAP in the spinal cord of US9 group was not significantly different from that of control group(P>0.05).2.3 In the US group,the results of detecting TNF-? and IL-1? in the serum of rats showed that there was no significant difference between the US1~US3 group and the BCP1 d group(P>0.05).There were significant differences in the content of the two inflammatory factors between the other ultrasound radiation groups and the corresponding model groups(P<0.01).For the inflammatory factor IL-6,the US5,US6 group and the US7~US9 group had lower levels in the serum of the rats compared with the corresponding BCP5 d and BCP10 d,and the difference was statistically significant(P<0.05).Among them,the serum levels of IL-6 cytokines in the US9 group were not significantly different from those in the control group(P>0.05).3.Clinical trial results of ultrasound radiation to alleviate cancer painAfter treatment,the cancer pain impact score,drug use,NRS score,and cancer pain relief rate were compared between the two groups.3.1 Cancer pain impact score: The impact of cancer pain on cancer patients was evaluated from six aspects: daily activities,emotions,walking ability,relationship with others,sleep and life enjoyment.The scores of the treatment group were lower than those of the control group.(P<0.01);3.2 Analgesic drug use: After the end of treatment,the dose of analgesic drugs in the control group was reduced to(15.78±9.663)mg,and the treatment group was reduced to(7.35±6.199)mg.The patients in the treatment group were treated with statistical analysis.The dosage of analgesic drugs was lower than that of the control group(P<0.01);3.3 NRS score: The NRS score of the control group decreased to 3.98±1.421,and the treatment group decreased to 2.35±1.440.The difference between the two groups was statistically significant(P<0.01).3.4 Cancer pain relief rate: The rate of cancer pain relief in the treatment group(88.24%)was 2.11 times that of the control group(41.82%)(P<0.01).Patients with cancer pain were stratified according to the degree of pain,and the rate of cancer pain relief in the patients with moderate to severe cancer pain at the end of treatment was calculated.The results showed that the pain relief rate of patients with moderate or severe cancer pain in the treatment group was higher than that of the control group.(P<0.01).Conclusions1.Using Walker256 cells to establish a rat model of bone cancer pain,and from the spontaneous pain score,mechanical paw withdrawal thresholds,tibial imaging test and HE staining,biochemical indicators(TNF-?,IL-1?,IL-6 and the expression of astrocyte marker Protein GFAP and microglia marker Protein IBA-1)were evaluated to achieve successful model establishment.2.After the intervention of ultrasound in the bone cancer pain model rats,the changes of the behavior and indicators related to cancer pain indicate that ultrasound can alleviate the pain symptoms of the model of bone cancer pain.And can effectively reduce the content of cancer-related indicators in rats;3.In the treatment group with ultrasound radiation,compared with the control group,the pain impact score,NRS score,and the amount of analgesic drugs were all decreased,and the cancer pain relief rate was also 2.11 times that of the control group.It is suggested that ultrasound as an adjuvant treatment can effectively alleviate the pain symptoms of patients with cancer pain,reduce the amount of analgesic drugs,and improve the quality of life of patients. |
PDF Full Text Request