Effect Of Intrathecal Morphine Analgesia On MOR Expression In Bone Cancer Pain Rats

Objective:Intrathecal low-dose morphine can achieve the same analgesic effect as oral or other peripheral routes of administration,and due to the smaller application dose,limited site of action,fewer side effects.Morphine analgesia acts on mu receptors,and mu opioid receptor(MOR)expression has been shown to be positively correlated with tumor progression.With the prolonged survival of cancer patients,cancer pain control therapy has gradually transformed into long-term analgesic therapy.In order to explore a more optimized administration mode for long-term cancer pain control using morphine,this experiment establishes an indwelling catheter for bone cancer pain SD rats and a long-term,multiple-dosing model.Compared with the peripheral administration group and the indwelling catheter administration group,the expression levels of MOR in tumor tissue and intrathecal tissue were different.Methods:1.To establish an available and stable rat bone cancer pain model.Five healthy female SD rats were prepared,and different concentrations of Walker256 tumor cells were implanted in their femoral cavities to explore the appropriate cell concentration for the establishment of femoral bone cancer pain in Walker256 tumor cells in SD rats.2.24 female Sprague-Dawley rats(150-180 g)were injected Walker256 carcinoma cells into the femur to produce a bone cancer pain model.after cancer pain model was successfully established,they were randomly divided into control group,intraperitoneal group and intrathecal group.The intrathecal group was placed intrathecal catheter in L6-S1 spinal spine space.The control group wasintraperitoneally injected with saline(1 ml,q.d.),intrathecal saline(20 μl,q.d.);the intraperitoneal group was intraperitoneally injected with morphine(1.25 mg/1 ml,q.d.),intrathecal injection of saline(20ul,q.d.);Intrathecal group was injected intraperitoneal saline(1ml,q.d.),intratheecal morphine(0.025mg/20 ul,q.d.)which has an equivalent dose with the intraperitoneal group,continuous analgesia for 16 days.Observed changes in pain threshold and spinal cord and tumor tissue MOR expression levels.Result:1.Successfully subcultured Walker256 rat tumor cells were implanted into the femur of rats and rat femur cancer pain model was successfully created.Rats with a cell concentration of 1×10 5 cells/body were the earliest and most stable cancer pain.The most obvious pathological changes,in the follow-up experimental species will use this cell concentration to establish bone cancer pain model.2.In the long-term administration model of femoral bone cancer pain SD rats,after analgesia,compared with the intraperitoneal group,the analgesic effect of the intrathecal group was similar.The expression of MOR in bone tumor tissues was significantly lower in the intrathecal group and control group than in the intraperitoneal group,P<0.05.There was no significant difference between the intrathecal group and control group,P>0.05.There was no significant difference in MOR expression between spinal cord tissue among control group,intrathecal group and intraperitoneal group,P>0.05.Immunohistochemical observation of the three groups of femoral tumor tissue sections,visible control group and intrathecal analgesia group,MOR expression levels were similar,P> 0.05.The expression of MOR in the intraperitoneal analgesia group was much higher than that in control group and the intrathecal analgesia group(P<0.05).In spinal cord sections,the expression of MOR in the three groups was relatively small,with no significant difference(P>0.05).Conclusion:1.During the process of making bone cancer pain model,it is found that the higherthe concentration of planting tumor cells is,the earlier the animal behavior changes are caused and the more stable the model is,the earlier the tumor may be generated,when the injected cell concentration is 1×105 cells/only,can establish the most stable rat bone cancer pain model.2.In the rat model of bone cancer pain,intrathecal long-term morphine analgesia can have analgesia similar to that of intraperitoneal morphine analgesia,and the expression of MOR in the tumor tissue is reduced,and the expression of MOR in the intrathecal group compared with the blank group is not.See significant differences.This may be due to the expression of morphine receptors in tumor tissues and its effect on local morphine concentrations.Controlling the concentration of peripheral morphine may lead to no significant increase in MOR expression in tumor tissues.There was no significant difference in MOR expression and MOR expression in the spinal cord between the intrathecal analgesia group and the tumor model blank group,indicating that intrathecal administration did not affect the expression level of MOR in the sheath and had little effect on receptor expression.Intrathecal morphine analgesia can achieve the same analgesic effect as peripheral intraperitoneal administration without affecting the expression level of MOR in the body through a small dosage,and may have little effect on tumor progression.