The Effects Of Persistent Pain On Breast Tumor Growth Established By Subcutaneous Transplantation In Wistar Rat

[Objectives] To investigate potential effect of persistent pain involved in breast tumor growth established by subcutaneous transplantation the mechanism of bone cancer in rats,and provide an ideal model to better understand the relationship between pain and cancer.[Methods] 1)With the female 160-190 g Wistar rats,the rats were randomly divided into three groups: Control group,Sham Operation group,and CCI Model(group chronic constriction Injury of sciatic nerve,CCI).In CCI group,chronic constriction Injury of sciatic nerve was used to simulate the neuropathic pain with cancer patients.The Sham Operation group was treated in the same way without sciatic nerve injury.After 4 days,we inoculated the ascites Walker256 breast cancer cells suspension(2×106 cells)in the left armpits for all groups.During the following 2 weeks,tumor diameter changes and the 50% paw withdraw mechanical threshold(PWMT)was monitored and the tumor weight was measured at the end of the experiment.2)The Wistar rats with the same standard mentioned above were randomly divided into three groups: Control group,Sham Operation group,and BCP Model group(Bone Cancer Pain,BCP).We inoculated into the upper tibia medullary cavity with the15 ul ascites Walker256 breast cancer cells suspension(5×104 cells)for BCP Model and the 15 ul PBS for the Sham Operation group.After 7 days,we adapted the xenograft tumor models for all groups.Tumor diameter changes,the 50%PMWT and tumor weight were measured as the same as the CCI model.3)Based on the completion of xenograft tumor in CCI model,the rats were randomly divided into Control+ Bupivacaine group,CCI+Saline Group(Normal Saline)and CCI +Bupivacaine group.The latter two groups were injected with 0.5% Bupivacaine hydrochloride(2.5ml/kg)and normal saline(2.5ml/kg)for a week from the fourth after tumor inoculation.The 50% PWMT was measured after administration of 0.5h 、 1h,2h,4h,8h,and 12 h.For the bone cancer pain with xenograft model,BCP +Morphine group and BCP+Saline Group were administrated morphine hydrochloride(3mg/kg)with the same volume normal saline.The 50% PWMT was measured with administration of pre0.5h,0.5h1 h,2h,3h and 4h.The other steps were operated as above mentioned.4)All the tumor issues were classified as three groups,control group,model group and medicine group;then operated for the formalin-fixed paraffin-embedded tissues and prepared for the analysis by Fourier transform infrared(FTIR)spectroscopy.[Results] In CCI Model group,the 50% paw withdraw mechanical threshold was lower on seventh days after CCI(p<0.05)and the tumor volume was larger(p<0.05)on tenth days after subcutaneous inoculation comparing with Normal Control group.Besides,the tumor weight of the CCI Model group was higher than that of the Control group(12.34±0.73 g VS 9.49±0.62g;P<0.05).However,the 50% PWMT was higher after the administration of 2h,4h and 8h(P<0.05)and the tumor weight of was also lower in contrast with White Control group(12.39±1.59 g VS 17.54±1.53g;p<0.05)when the CCI+ Bupivacaine group rats was injection bupivacaine subcutaneously.In Bone Cancer Pain model,we also observed the 50% PWMT was lower on eleventh days after BCP(P<0.01)and the tumor volume was larger on tenth day and fourteenth day after subcutaneous inoculation of(P<0.05).the tumor weight of the BCP Model group was higher than that of the Control group(5.68±0.42 g VS 3.37±0.52g;P<0.05).After the administration morphine hydrochloride of 0.5h,1h and 2h,the 50% PWMT was higher(P<0.05)and the tumor weight of the BCP+ Morphine group was lower than that of the BCP+Saline group(6.37±0.54 g VS 8.02±0.25g;p<0.05).4).There is no difference in biomolecular peak among the three groups of both CCI Model rats and BCP Model rats.[Conclusion] Subcutaneous transplantation in Wistar rat with persistent pain mimic the condition of the tumor itself under the effect of persistent pain well.Meanwhile,the effective pain relief can weaken this negative stimulation impact to some extent.Our data suggest that Long-term pain is not just a symptom,but also a contributing factor for the growth of breast cancer in rats.