Study on the analgesic effects of icaritin in combination with morphine on bone cancer pain in mice
Objective:This study aimed to investigate the analgesic effect of icaritin on bone cancer pain(BCP)in mice and the potential synergistic analgesic effect of icaritin and morphine.Additionally,we sought to determine the extent of morphine dose reduction when icaritin was administered at a half-effective dose in combination with morphine.Methods:We established a mouse model of BCP using male C57BL/6J mice and lewis lung carcinoma(LLC)cells.We assessed the pain threshold by measuring the mechanical withdrawal threshold(MWT)in response to mechanical stimulation,the paw withdrawal latency(PWL)in response to cold stimulation,the frequency of spontaneous flinches,and the time spent guarding.Results:Between the 7th and 14th days after modeling,BCP mice exhibited a significant decrease in MWT and PWL in the ipsilateral(tumor-bearing)hind paw,along with a significant increase in spontaneous flinches and time spent guarding(P<0.05).Icaritin was administered from the 7th to the 14th day after modeling.Starting from the 10th to the 14th day,icaritin significantly increased MWT and PWL in the ipsilateral hind paw of BCP model mice,while reduced the frequency of spontaneous flinches and the time spent guarding.These analgesic effects persisted until the 18th day after surgery(i.e.,the 4th day after drug discontinuation)(P<0.05).When icaritin was administered at a dose of 2×EC50(200 mg/kg)in combination with morphine,it significantly prolonged the post-analgesic effects after drug discontinuation,with these effects lasting until the 21st day after surgery(i.e.,the 7th day after drug discontinuation)(P<0.05).Furthermore,when icaritin was administered at a half-effective dose(100 mg/kg)in combination with morphine,it reduced the required morphine dosage by up to 60%while maintaining the best analgesic effect achievable with morphine.Conclusion:Icaritin exhibits a significant analgesic effect on bone cancer pain in mice.When combined with morphine,icaritin not only prolongs post-analgesic effects after drug discontinuation but also reduces the required morphine dosage by up to 60%.
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维普
