选择性神经损伤模型所致神经病理性疼痛对小鼠肠道菌群多样性的影响

Effects of neuropathic pain induced by selective nerve injury model on intestinal microflora diversity in mice

目的探讨选择性神经损伤(selective nerve injury,SNI)模型所致神经病理性疼痛对C57小鼠肠道菌群多样性的影响。方法将36只C57小鼠进行随机分组,分别为SNI模型组、假手术组和对照组(n分别为18、8、10)。分别在造模后0、1、3、7、14 d进行机械刺激痛阈和热痛敏测试;在造模后第14天取所有小鼠结肠末端内容物(新鲜粪便)分析其肠道菌群多样性。结果造模后1 d,SNI模型组小鼠由于神经损伤致机械刺激痛阈较造模前显著下降(超过70%)、热痛敏阈值下降40%,而假手术组和对照组无显著下降,SNI模型组表现为患足痛觉过敏,与假手术组和对照组相比,差异具有统计学意义(P<0.001);假手术组在造模后第1天热痛敏阈值较对照组出现短暂下降(P=0.006),但第3天之后两组间痛阈变化无差异。α-多样性分析显示,SNI模型组肠道菌群Observed、Chao1、ACE和Simpson等丰度明显低于对照组(P<0.05),即SNI模型组由于疼痛刺激出现了菌群紊乱;而假手术组肠道菌群各丰度均低于对照组(P<0.05),下降变化介于SNI模型组和对照组之间。结论SNI模型所致神经病理性疼痛导致C57小鼠机械刺激痛阈和热痛敏阈值下降,使其肠道菌群多样性降低。

Objective To investigate the effects of neuropathic pain induced by selective nerve injury(SNI)on intestinal microflora diversity in C57 mice.Methods 36 C57 mice were randomly divided into SNI model group(n=18),sham-operation group(n=8),and control group(n=10).At day 0,1,3,7,and 14 after modeling,mechanical pain threshold and thermal pain sensitivity tests were carried out.At day 14 after modeling,colon content(fresh feces)from all the mice were collected for intestinal microflora diversity analysis.Results One day after modeling,the mechanical pain threshold in SNI group decreased significantly(more than 70%)due to nerve injury,and the thermal pain threshold decreased by 40%,while sham group and control group had no significant decrease.SNI group showed foot hyperalgesia,and the difference was statistically significant compared with sham group and control group(P<0.001).Compared with control group,sham-operation group had a transient decrease in thermal pain threshold on the first day after modeling(P=0.006),but there was no difference in pain threshold between the two groups on the third day after modeling.Theα-diversity analysis showed that the abundance of Observed,Chao1,ACE and Simpson in SNI group was significantly lower than that in control group(P<0.05).That is,SNI group had flora disorder due to pain stimulation.Observed,Chao1,ACE,and Simpson were less abundant in sham group than in control group(P<0.05)and the change was between SNI group and control group.Conclusion Neuropathic pain induced by SNI model resulted in the decrease of mechanical pain threshold and thermal pain threshold,which leads to the reduction of intestinal flora diversity in C57 mice.