The Preliminary Research Of Various Chemical-Induced Breakthrough Cancer Pain In Mice

Objective:To establish the morphine analgesia model of C57BL/6bone cancer pain mice. To observe the changes of pain behavior in the morphine analgesia mice by injection of ET-1.To investigate the possibility of ET-1induced breakthrough cancer pain model.Methods:(1)Twenty adult male C57BL/6mice, randomly divided into two groups(n=10):cancer pain group:2×106Lewis lung cancer cells in10ul D-Hank’s were injected into the left femur bone marrow cavity; control group:injection of10ul D-Hank’s. Limb use score and voluntary wheel running test were measured throughout the experiment.(2)Forty-two adult male C57BL/6mice, randomly divided into seven groups(n=6):14,16,21days after injection of LLC, each group was intraperitoneally injected with morphine at the concentration of5、10、40mg/kg respectively. Spontaneous lifting scores were measured after1h later.(3)Eighteen adult male C57BL/6cancer pain mice, given good effect of morphine analgesia and similar pain behavior, were randomly divided into three groups (n=6):Duble distilled water group, ET-1(75pmol) group, ET-1(150pmol) group, Acid (pH=4) group, Acid (pH=5) group, Soda (pH=8) group. Drugs were directly injected into tumor locally in all groups. Then spontaneous lifting scores were measured immediately.(4)Eighteen adult male C57BL/6mice, randomly divided into three groups:normal group, morphine group, cancer pain group. Normal group were given Intramuscular injection of150pmo ET-1, the other two groups were given tumor locally injection of the same dose of ET-1. Spontaneous lifting score was measured during the next1hour.Results:(1)Spontaneous lifting scores were significantly decreased in cancer group as compared to the sham group in day12while numbers of flinches were significantly increased. Times of flinches were significantly increased in cancer group as compared to the sham group in day9while distance traveled was significantly decreased.(2)There was no significant difference between morphine dose of day14group and 5mg/kg of day16group. In day16group and day21group, the spontaneous lifting score was significantly increased after morphine injection intraperitoneally.(3)There was no significant difference in double distilled water group and ET-1(75pmol) group, Acid (pH=5) group, Soda (pH=8) group. The spontaneous lifting score was significantly decreased by injection of ET-1(150pmol) and Acid (pH=5).(4)The spontaneous lifting scores were decreased with different degree during the first40mins in the cancer pain group after injection ET-1.Conclusion:(1) Both Limb use score and Voluntary wheel running test can evaluate the spontaneous behavior of bone cancer pain in mice.(2) Intraperitoneally injection of morphine can effectively control the background pain in mice.(3) Tumor locally injection of150pmol ET-1is the minimum effective dose to induce breakthrough cancer pain.(4) The appearance of peak time for breakthrough cancer pain after injection of ET-1is in5min and the duration is in30min, which was similar with the Characteristics of the clinical incident of BTCP patients.