Xiaomei Wang,1,2 Yinsheng Chen,3 Shuwen Qian,4 Jia Kong,2 Zehua Su,5 Qingxiu Wang,3,* Lijun Liao5,* 

1Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Department of Anesthesiology Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3Shanghai East Hospital Clinical Medical College, Nanjing Medical University, Shanghai, People’s Republic of China; 4Department of Anesthesiology and Pain Management, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 5Department of Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Qingxiu Wang, Shanghai East Hospital Clinical Medical College, Nanjing Medical University, No. 1800, YunTai Road, Shanghai, 200123, People’s Republic of China, Tel +86 13310054121, Email qxw1123@126.com Lijun Liao, Department of Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, No. 1800, YunTai Road, Shanghai, 200123, People’s Republic of China, Tel +86 13817428913, Email liao@pan-intelligence.com

Purpose: Compound probiotics have been reported to ameliorate imbalances in the intestinal flora that may play a critical role in neuropathic pain. This study aimed to investigate the efficacy of compound probiotic treatment on neuropathic pain.
Methods: Thirty mice were randomly divided into three groups: 1) sham group, 2) mouse with chronic constrictive injury (CCI), and 3) probiotic gavage with CCI (CCI+Prob). The degree of pain and gait recovery was assessed by Mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), and mouse footprints. The degree of atrophy of the gastrocnemius muscle was assessed by muscle weight, hematoxylin and eosin (H&E) staining. Gut microbiota were analyzed by 16S ribosomal RNA sequencing (16SrRNA).
Results: Four weeks after surgery, TWL and MWT assessment showed significant increases in the CCI+Prob group compared with the CCI group (P < 0.01). Gait analysis results as well as gastrocnemius muscle weight showed a significant improvement in the CCI+Prob group compared with the CCI group. Measurement of alpha diversity showed a significant increase in the CCI group compared with the sham group, but this increase was attenuated by probiotic intervention in the CCI+Prob group. Although the CCI group had significantly decreased levels of Akkermansia and significantly increased levels of Ruminococcaceae, probiotic treatment reversed these changes.
Conclusion: Compound probiotics treatment can improve the pain and muscle atrophy in mice with CCI-induced neuropathic pain. The improvement of symptoms is associated with changes in the composition of gut microbiota.

Keywords: probiotics, neuropathic pain, gut microbiota, muscle atrophy, Akkermansia, Ruminococcaceae