骨癌痛大鼠钠通道Nav1.8的表达与行为学变化
Expression of sodium channel Nav1.8 and behavioral changes of rats with bone cancer pain

目的 观察钠通道Nav1.8在Walker256乳腺癌细胞所致胫骨骨癌痛大鼠背根神经节（DRG）及丘脑中的表达变化，探讨Nav1.8与癌痛的相关性。 方法 将Wistar大鼠随机分为癌痛组（n=15）和假手术组（n=15）。在癌痛组大鼠胫骨内注入密度为107/mL的Walker256乳腺癌细胞,建立骨癌痛模型；假手术组在大鼠胫骨内注入相同体积的生理盐水。术后8、11、14、17、21 d评估机械性异常性疼痛和热痛觉过敏。造模21d进行影像学检查后，取其DRG及丘脑组织，荧光实时定量RT-PCR观察Nav1.8 mRNA 在DRG和丘脑中的表达变化，免疫荧光观察Nav1.8蛋白在DRG中的表达。 结果 癌痛组大鼠术后各时间点出现了明显的机械性痛觉过敏，机械性缩足阈值与术前和假手术组比较，差异有统计学意义（P<0.05）；术后癌痛组热刺激缩足反射潜伏期无显著变化，与术前及假手术组比较，差异无统计学意义（P>0.05）。Nav1.8 mRNA在手术侧DRG及手术对侧丘脑中的表达明显上调（P<0.05）；手术对侧DRG和同侧丘脑中的Nav1.8 mRNA与假手术组比较，差异无统计学意义（P>0.05）。 结论 Nav1.8的表达上调与大鼠骨癌痛的发生有一定关系。
： Objective To observe the expression changes of sodium channel Nav1.8 in dorsal root ganglion (DRG) and thalamus of rats with tibial cancer pain caused by Walker256 mammary gland carcinoma cells and explore the correlation of Nav1.8 and cancer pain. Methods Wistar rats were randomly divided into the bone cancer pain group (n=15) and sham-operation group (n=15). The bone cancer pain model was established by injecting the Walker256 mammary gland carcinoma cells of 107/mL into the tibia medullary cavity of rats of the bone cancer pain group. The tibia medullary cavity of rats of the sham-operation group was injected with the same volume of normal saline. The mechanical withdraw threshold and paw withdrawal thermal latency were assessed 8, 11, 14, 17, and 21 d after surgery. Imaging examination was conducted 21 d after surgery and DRG and thalamus of rats were collected. Expression changes of Nav1.8 mRNA in DRG and thalamus were observed by the real-time PCR. The protein expression of Nav1.8 in DRG was detected by the immunofluorescence method. Results The mechanical hyperalgesia of the bone cancer pain group was significant at each time point after surgery. Compared with sham-operation group and before surgery, the differences of mechanical withdraw threshold were statistically significant (P<0.05). The paw withdrawal thermal latency of the bone cancer pain group did not change significantly after surgery. The differences of paw withdrawal thermal latency of the sham-operation group and bone cancer pain group after surgery and before surgery were not statistically significant (P>0.05). The mRNA expressions of Nav1.8 in operation homolateral DRG and operation contralateral thalamus were significantly increased (P<0.05). The differences of mRNA expressions of Nav1.8 in operation contralateral DRG and operation homolateral thalamus of the bone cancer pain group and sham-operation group were not statistically significant (P>0.05). Conclusion The up-regulation of Navl.8 expression is relevant to the