Abstract: Objective To observe the anxiety-like behavior and the change of gut microbiota in aged mice with chronic neuropathic pain-related anxiety. Methods The male C57BL/6 mice aged 16 months were randomly divided into model group and control group, with 6 mice in each group. Spared nerve injury (SNI) surgery was performed in the sciatic nerve to establish neuropathic pain-related anxiety model. On the 21st day after surgery, Von-Frey hairs test was used to detect mechanical hyperalgesia. The open field test (OFT) and elevated plus maze (EPM) experiments were used to detect anxiety-like behaviors. 16S rDNA sequencing was used to analyze the gut microbiota. Results The mice in the model group showed decreasing mechanical thresholds in the Von Frey test (P<0.001). On the 21st day after SNI, the activity time of the mice entering the central area of OFT and the open arm area of EPM experiments were significantly less than those of the control group(P<0.05), suggesting that SNI mice had anxiety-like behaviors. The total distance of the model group and the control group in OFT and EPM experiments showed no significant difference. The analysis of gut microbiota showed that the gut microbiota structure in the SNI mice was disordered and the diversity of the flora was reduced. In the SNI mice, 2β-proteobacteria were significantly reduced at the level of phylum classification, Lactobacillus was significantly reduced at the order level, and Prevotella was significantly reduced at the family level. Conclusions Aged mice with neuropathic pain-related anxiety have anxiety-like behaviors and show significant changes in gut microbiota.

Key words: aged mice, pain, anxiety, gut microbiota