Withdrawal Response And Mechanism Of Sufentanil And Morphine In Analgesia Of Rats With Bone Cancer Pain

Objective:To observe the withdrawal response and mechanism of sufentanil and morphine in analgesia of bone cancer pain rats.Methods:1.Wistar young mice were intraperitoneally inoculated with Walker256 rat breast cancer cells.After the occurrence of cancerous ascites,ascites were extracted and the cell morphology was observed under a microscope.58 healthy adult female SD rats,weighing 200-220g,were randomly divided into Sham group(Sham,n=10)and bone cancer pain group(BCP,n=48).The left tibia of Sham group was inoculated with 10 ul inactivated walker256 rat breast cancer cells,and the left tibia of BCP group was inoculated with 10ul(1-3)10~7 cells/ml walker256 rat breast cancer cells.The mechanical withdrawal threshold(MWT)was measured before modeling(d0)and at day 3,6,9,and 12after modeling(d3,d6,d9,d12).Two hours after the pain threshold was measured on day 12,three pathological sections of rats in the sham operation group and bone cancer pain group were randomly selected for HE staining to determine whether the bone cancer pain model was successfully established.2.38 SD rats with bone cancer pain successfully modeled were selected and randomly divided into Control group of normal saline,Morphine group and Sufentanil group,10 rats in Control group?13 rats in Morphine group and 15 rats in Sufentanil group.Three groups of rats at the same time every day(12:00 noon,evening 20:00)subcutaneous injection of physiological saline respectively,morphine 15 mg/kg,and sufentanil 15ug/kg,respectively(d0),1 day before delivery to the medicine after 1,3,5,7,9 days(d1,d3,d5,d7,d9)in 30 min after dosing to determine each group rats mechanical shrink enough reaction threshold,the last time for 2 h after each group of randomly selected from4 only take the nucleus accumbens in rats in the liquid nitrogen frozen deposit reserve;Other rats were injected with naloxone hydrochloride(4mg/kg)intritoneally to induce withdrawal.The wet-dog-like shaking,jumping,standing,dental fibrillation and weight change within 1 hour after withdrawal were observed in each group within 15 minutes after induction of withdrawal.The nucleus accumbens was taken and stored in liquid nitrogen for later use 2 hours after observation of withdrawal reaction.RT-qPCR was used to detect the expression of dopamine D3receptor mRNA in nucleus accumbens.Results:1.After the preparation of the tibial bone cancer pain model,the mechanical pain threshold of the rats in the BCP group was significantly lower than that in the sham operation group on the 9th day and the 12th day,and the difference was statistically significant(P<0.05),The pathological sections of the BCP group showed trabecular fracture and malignant tumor cell infiltration by HE staining?2.Before administration,there was no significant difference in the basic mechanical pain threshold between the three groups(P>0.05).On the first day,the third day and the fifth day after administration,there was no statistical difference between the mechanical pain threshold of the Control group and the basic mechanical pain threshold(P>0.05).Sufentanil and Morphine groups had significantly higher mechanical pain threshold than the Control group and the first day before administration,and the difference was statistically significant(P<0.05).On the 7th and9th days after administration,there was no statistical difference between the mechanical pain threshold of the Control group and the basic mechanical pain threshold(P>0.05),and no statistical difference between the mechanical pain threshold of the Sufentanil group and Morphine group and that of the concurrent group and the first day before administration(P>0.05).3.Sufentanil,Morphine,two groups of rats with naloxone(4 mg/kg)urged all have withdrawal symptoms after withdrawal,withdrawal reactions score higher than the Control group,the difference was statistically significant(P<0.05),Sufentanil,Morphine,two groups of rats body weight more than in the Control group,the difference was statistically significant(P<0.05),Sufentanil group the Morphine withdrawal reaction in rats score is low,the difference was statistically significant(P<0.05),Morphine group had less weight loss,with a statistically significant difference(P<0.05).4.There was no significant difference in the expression level of D3DR mRNA between the Control group,Sufentanil group and Morphine group before withdrawal(P>0.05).There was no significant difference in the expression level of D3DR mRNA between the Control group,Sufentanil group and Morphine group(P>0.05).There was no significant difference in the expression level of D3DR mRNA between the Control group before and after withdrawal(P>0.05).Sufentanil group showed no significant difference in the expression level of D3DR mRNA before and after withdrawal(P>0.05).Morphine group showed no significant difference in D3DR mRNA expression before and after Morphine withdrawal(P>0.05).Conclusion:1.Both sufentanil and morphine have analgesic effect on bone cancer pain rats.2.Similar to morphine,sufentanil showed tolerance and dependence when used for analgesia in rats with bone cancer pain,both of which developed tolerance on the seventh day,but sufentanil was less physically dependent than morphine.3.Sufentanil and morphine withdrawal response were not related to the expression level of D3DR mRNA in nucleus accumbens.Figure 8,table 1,33 references.