The Effect Of Morphine On The Expression Level Of MOR And Microvessel Density In A Rat Bone Cancer Pain Model

Objective To evaluate the feasibility of establishing bone cancer pain model by inoculating Walker 256 breast cancer cells into tibia of Sprague Dawley female ratsMethods Eighteen clean Sprague-Dawley adult female rats were randomly divided into three groups:blank group(n=6),sham operation group(n=6),and cancer pain group(n=6).The bone cancer pain model was prepared by injecting 15?lx105/ml Walker256 rat carcinoma cells into the bone marrow cavity about lcm under the tibia platform of the right hind limb.The body weight of the rats and the mechanical pain threshold by pain ethology were measured on the modeling day and on day 3,6,9,12,14 after modeling.The tumor tissue was taken out for histological examination 14 days after modelingResults In this part of the study,it was found that the SD rat tibia bone cancer pain model was successfully prepared by Walker256 rat breast cancer cells.At each time point after the day 6 of modeling,there was no significant difference in mechanical pain threshold of right hind limb between sham group and blank control group(P>0.05).Compared with the blank control group and sham operation group,the mechanical pain threshold of right hind limb of cancer pain group decreased at all time points,and the difference was statistically significant(P<0.05).Compared with the blank control group and the sham operation group,in the bone cancer pain group,the bone marrow cavity was destroyed obviously,and there were bone and trabecular bone structure destroyed.The bone marrow cavity is filled with a large number of tumor cells.It can be seen that cancer cells infiltrate outward through the damaged bone marrow cavityConclusion Walker 256 breast cancer cells can successfully establish a diabetic bone cancer pain model in ratsObjectiveThe analgesic effect of different doses of morphine in SD rat bone cancer pain model was evaluated by measuring mechanical pain threshold.and the effects of morphine on tumor progression were initially explored by examining the expression of MOR and microvessel density in tumor tissuesMethodsClean-grade adult female SD rats were selected for experiments.After walker 256 breast cancer cells were used to successfully establish a bone cancer pain model,the modeled 24 rats were divided into 3 groups by random number table method:MO group[normal saline(NS)control cancer pain group]8 mice,M1 group(3mg/kg morphine cancer pain group)8 mice,M2 group(6mg/kg morphine cancer pain group)8 mice,and 8 normal rats were selected as blank controls group(Group C).Intraperitoneal injection is performed at 9:00 AM daily for 21 consecutive days.The morphine dose was calculated according to the weight of the rats in the experimental group,and morphine was diluted with NS to 1ml volume for intraperitoneal injection.The control group was directly injected with 1 ml of NS.The mechanical pain threshold was measured 30 minutes after intraperitoneal injection in all rats.After 21 days of continuous intraperitoneal injection,the rats were sacrificed after inhalation anesthesia,and The tumor tissue of the right hind limb tibia was removed for HE staining.The expression level of MOR in tumor tissues was determined by Western Blot immunohistochemical staining was used to measure the positive rate of CD31 in tumor tissues and microvascular density(MVD)was measured by hot spot countingResults1.Morphine increases the threshold of mechanical pain in the right hind limbThe threshold of mechanical pain in the right hind limb of the rats in group M1 and M2 is close to that in group C(P>0.05);The threshold of mechanical pain in the right hind limb of the M1 and M2 rats was significantly higher than that of the M0 group(P<0.05);The threshold of mechanical pain in the right hind limb of M1 group rats reached the same level as that of M2 group(P>0.05)2.Morphine increases the level of MOR expression in tumor tissuesThe expression level of MOR in tumor tissues of M0 group,M1 group and M2 group was significantly higher than that of C group(P<0.05);The expression level of MOR in M1 and M2 groups was higher than that in M0 group(P<0.05);The expression level of MOR in M2 group was higher than that in M1 group(P<0.05)3.Morphine increases MVD expression in tumor tissuesThe expression levels of MVD in tumor tissues of M0,M1 and M2 groups were significantly higher than those of C group(P<0.05);The MVD value in tumor tissues of M1 and M2 groups was higher than that of M0 group(P<0.05).The MVD value of tumor tissue in M2 group was higher than that in M1 group(P<0.05)Conclusion In the pain model of bone cancer of rat,morphine probably promotes microangiogenesis in tumor tissues by up-regulating the expression of MOR in tumor tissues.