| Background and purpose:Bone cancer pain is a common symptom of advanced cancer in patients.About 40%of patients with cancer pain were not effectively controlled and had poor quality of life,due to the addiction,tolerance and adverse reactions result from effective opioids like morphine.As a kind of traditional Chinese medicine,scorpion had a good analgesic effect.We studied the analgesic effect of scorpion on rat tibial with cancer pain and its mechanism about activation of astrocytes and micoglia in spinal dorsal horn The purpose of this study is to investigate the analgesic effect of scorpion on cancer pain and its mechanism.Methods:We established rat models of cancer-induced bone pain,which were randomly divided into sham operation group,cancer group,scorpion prophylaxis group and scorpion therapeutic group,with 10 rats in each group.The weight of rats was measured every other day.Measurement indicators included 50%paw withdraw threshold(PWT)which was measured by up-and-down method in von-Frey hair and the spontaneous ambulatory pain score(SAPS)method.On the fourth day after modeling,rats in scorpion prophylaxis group were given gavage twice daily for 0.54g/kg for 17 days.On the 14th day after modeling,scorpion therapeutic group was given gavage twice a day at a dosage of 0.54g/kg for 7 consecutive days.On the 21th day after modeling,tibial radiographs were shot.Spinal cord astrocyte marker GFAP and microglial marker Iba1 was detected by Western Blot and immunofluorescence.TNF-α,IL-6 and IL-1β in rats was discovered by Real-time PCR.The effect of scorpion aqueous extract on the proliferation of Walker 256 rat mammary gland carcinoma cells in vitro was evaluated by CCK8 assay.Results:1.On the fifth day after establishing the model of ascites tumor by injecting 2 ×105 Walker 256 rat mammary gland carcinoma cells in the left tibial cavity of the rat,compared with sham operation group,the 50%PWT and spontaneous pain score decreased significantly.Compared with cancer group,50%PWT and spontaneous ambulatory pain score increased in scorpion prophylaxis group and scorpion therapeutic group,respectively.Except for sham operation group,hyperalgesia was observed in other three groups.Compared with the cancer group,the extent of bone destruction in sham operation group,scorpion prophylaxis group and scorpion therapeutic group had lesser extent significantly.2.Immunofluorescence showed that astrocytes and microglia in the dorsal horn of spinal cord were activated and increased significantly in the cancer group,scorpion prophylaxis group and scorpion therapeutic group.Compared with cancer group,scorpion prophylaxis group and the scorpion therapeutic group had lower activation degree and smaller number of astrocytes and microglia significantly.Compared with cancer group,the expression of GFAP(marker of glial fibrillary acidic protein)and Iba1(marker of microglial marker protein)were lower in the sham-operated group,prophylactic scorpion-administered group and scorpion-treated group significantly.3.Compared with the cancer group,the expression of TNF-α,IL-6 and IL-1βmRNA were lower in sham operation group,scorpion prophylaxis group and scorpion therapeutic group,respectively.4.Scorpion inhibited proliferation of Walker 256 rat mammary gland carcinoma cells in a concentration-dependent manner.Conclusion:1.When bone cancer pain occured,scorpion may play an analgesic effect both for prophylactic or therapeutic administration,and its mechanism may be explained by inhibiting the activation of astrocytes and microglia in the spinal dorsal horn and reducing secretion of neuroinflammatory cytokines including TNF-α,IL-6 and IL-1β.2.Scorpion had not only anti-tumor effect by inhibiting proliferation of Walker 256 rat mammary gland carcinoma cells in vitro,but also analgesic effect via reducing the extent of bone destruction. |
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