| ObjectiveTo explore the withdrawal reaction of hydromorphine hydrochloride on tibial cancer pain and its possible mechanism.Methods1.Wistar young rats were inoculated intraperitoneally with Walker256 rat breast cancer cells.After carcinomatous ascites,ascites was extracted and the morphology of the cells was observed under microscope.The cell density was adjusted to(1? 3)× 10 ~ 7 cells / ml by PBS.38 healthy adult female SD rats weighing 200? 220 g were randomly divided into two groups: sham operation group(Sham,n = 11)and bone cancer pain group(BCP,n=27).The left tibia of rats in sham operation group was inoculated with 10 ? l inactivated walker256 rat breast cancer cells.Left tibia inoculation in painful group of bone cancer The concentration of 10 ? l was(1)× 10 7 cells / ml in Walker256 rat breast cancer cells.The mechanical pain threshold(mechanical withdrawal threshold,MWT)was measured before(d 0)and at day 1,3,5,7,9,11(d 1,d 3,d 5,d 7,d 9,d 11)before modeling(d 0)and at 1,3,5,7,9,11 days after injection.On the 12 th day,3 rats of sham operation group and model group of bone cancer pain were randomly selected for HE staining to confirm whether the model of bone cancer pain was successful or not.2.24 SD rats with bone cancer pain were randomly divided into three groups: hydromorphine group(Hyd group),morphine group(Mor group)and saline group(NS group),with 8 rats in each group.Morphine dependence model was established in morphine group by subcutaneous administration of morphine 3 times a day for 7 days,and hydromorphine dependence model was established in hydromorphine group by equivalent dose of morphine.Naloxone hydrochloride(4 mg / kg,intraperitoneal injection)was used to urge withdrawal 8 hours after the last administration,and the saline group was replaced by the same volume of saline.1 day before(d 0)and 1,2,3,4,5 after administration,respectively.On the 6th day(D1,D2,d3,d4,d5,d6),the threshold value of mechanical pain(MWT)was measured 30 minutes after administration.The abstinence symptoms(such as wet dog-like shaking,jumping,standing,tooth tremor)were observed at 15 minutes after withdrawal by 1min,and the body weight was measured 1 hour later.The expression of Glu-2 subunit of AMPA receptor in nucleus accumbens was detected by Western blot(western blot,WB)after deep anesthesia and cryopreservation of nucleus accumbens(Nucleus accumbens)in liquid nitrogen.Results1.Before the establishment of bone cancer pain model,there was no significant difference in basal weight between(BCP)group and(Sham)group(P > 0.05).After modeling,the body weight of the sham operation group continued to gain,while the weight gain of the tibial cancer pain group was slower than that of the control group.On the 3rd,6th and 9th day after operation,there was a significant difference between the two groups(P < 0.05).There was no significant difference in mechanical pain threshold between bone cancer pain group and sham operation group from the first day after modeling,and there was no significant difference between the two groups.But with the recovery of the surgical wound,the threshold of mechanical pain in the sham operation group gradually increased from the 5th day.The mechanical pain thresholds of the two groups were significantly different on the 5th,7th,9th and 11 th day after the establishment of the model(P < 0.05).2.After the model of bone cancer pain was successfully established,there was no significant difference in baseline pain threshold between hydromorphin(Hyd)group,morphine(Mor)group and normal saline(NS)group before administration(P > 0.05).On the first day of administration,the mechanical pain threshold of hydromorphine(Hyd)group and morphine(Mor)group was significantly higher than that of physiological saline group(P < 0.05).On the 1st,2nd,3rd day of administration,the mechanical pain threshold of the(Hyd)group was significantly higher than that of the control group(P < 0.05),and on the 1st,2nd,3rd,4th day,the mechanical pain threshold of the morphine(Mor)group was significantly higher than that of the morphine group(P < 0.05).The mechanical pain threshold was significantly higher than that before and before administration(P < 0.05).On the 4th day of administration,the pain threshold decreased in the hydromorphine group,while the pain threshold in the morphine group began to decrease on the 5th day.3.After administration of naloxone hydrochloride,compared with NS group,the scores of withdrawal symptoms in Mor group and Hyd group were higher than those in Hyd group(P < 0.05),and there was significant difference in weight loss between Hyd group and Mor group(P < 0.05).Compared with Hyd group,the weight loss in Mor group was more significant(P < 0.05),the difference was statistically significant(P < 0.05),but there was no significant difference in withdrawal score between the two groups(P > 0.05).4.After withdrawal induced by naloxone hydrochloride,the expression of Glu-2 protein in nucleus accumbens of Hyd group was up-regulated compared with that of NS group(P < 0.05),and the expression of Glu-2 protein in nucleus accumbens of Hyd group was up-regulated compared with Hyd group(P < 0.05).There was no significant difference in the expression of Glu-2 protein between the).Mor group and the NS group(P < 0.05).There was no significant difference in the expression of Glu-2 protein between the two groups(P > 0.05).Conclusion 1.Both hydromorphine and morphine have analgesic effects on rats with bone cancer pain.2.Like morphine,hydromorphine is tolerant and dependent in analgesia in rats with bone cancer pain,and hydromorphine tolerance is earlier than that in morphine.3.After withdrawal induced by naloxone Hydrochloride for 7 days,withdrawal symptoms also occurred in rats with cancer pain,which could up-regulate the expression of Glu-2 subunit of AMPA receptor in nucleus accumbens of rats.These results suggest that AMPA receptors in the synapses of nucleus accumbens may play an important role in opioid withdrawal and participate in the withdrawal response of opioids. |
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