神经生长因子在骨癌痛大鼠DRG的变化及其对疼痛行为学的影响

CHANGES OF NERVE GROWTH FACTOR IN THE DORSAL ROOT GANGLION NEURONS OF RATS WITH BONE CANCER PAIN AND ITS EFFECTS ON PAIN-RELATED BEHAVIORS

目的:检测骨癌痛大鼠背根神经节(DRG)神经生长因子(NGF)及其受体TrkA及P75的表达,并观察鞘内注射抗神经生长因子抗体(anti-NGF)对骨癌痛大鼠疼痛行为学的影响,探讨NGF在骨癌痛中可能的作用。方法:建立大鼠胫骨骨癌痛模型,观察疼痛行为学变化,造模21天,检测大鼠DRG神经元NGF、TrkA及P75蛋白及mRNA表达;并进一步将骨癌痛大鼠分成cancer及cancer+anti-NGF组,观察anti-NGF对骨癌痛大鼠疼痛行为学的影响。结果:接种侧DRG神经元NGF及其受体在骨癌痛大鼠的表达明显高于sham组;cancer组大鼠的PWL缩短,PWT降低,鞘内使用anti-NGF后PWL延长,PWT增高。结论:NGF加剧大鼠骨癌痛,anti-NGF在骨癌痛中具有明显的抗伤害感受作用。

Objective：To determine the expression of nerve growth factor（NGF） and its receptors（TrkA,P75） in L4/L5 dorsal root ganglia（DRG） of rats with bone cancer pain,and anti-NGF were administered intrathecally at 16～21 days after implantation to observe the changes of pain-related behavior.To investigate the potential role of NGF on bone cancer pain in rats.Methods： Bone cancer pain was induced by implantation of Walker 256 breast carcinosarcoma cells into the tibia.After surgery,mechanical and thermal hyperalgesia and ambulation scores were evaluated to identify pain-related behavior.Western blotting and fluorescent quantitation real-time RT-PCR were used to determine NGF,TrkA,P75 protein and mRNA expression in ipsilateral L4/L5 DRG at 21 days after surgery between tumor-bearing and sham rats.Anti-NGF were administered intrathecally at 16～21 days after surgery to compare the changes in pain-related behavior.Results： Western-blot and real-time RT-PCR showed that the total expression of NGF,TrkA,P75 protein and mRNA levels significantly increased in ipsilateral L4/L5 DRG of cancer rats compared with the sham group.Cancer rats exhibited mechanical and thermal hyperalgesia from day 13 after implantation of Walker 256 cells,and cancer rats also showed alleviated mechanical hyperalgesia and ambulatory-evoked pain after administration of anti-NGF intrathecally.Conclusion： NGF is involved in the development of bone cancer pain.Intrathecal anti-NGF significantly attenuates bone cancer-caused hyperalgesia.