Rui-Feng Ao,1 Heng-Rui Yong,1 Ying-Tao Hu,1 Yu-Sheng Huang,1 Jia-Wen Gao,1 Chen Tu,1,2 Jing-Shen Zhuang,1 Zhao-Ming Zhong1 

1Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Orthopedics, Academy of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China

Correspondence: Jing-Shen Zhuang, Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Email zjs119@smu.edu.cn Zhao-Ming Zhong, Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Email zhongzm@smu.edu.cn

Background: Chronic pain is a global health issue that affects as many as 20% of the population. Inflammatory pain, an important form of chronic pain, negatively impacts patients’ quality of life. Indolepropionic acid (IPA), a metabolite derived from the gut microbiota, has anti-inflammatory properties. However, its effect on inflammatory pain has not yet been explored. This study aims to investigate the impact of IPA on CFA-induced inflammatory pain.
Methods: A mouse model of inflammatory pain was established by injection of Complete Freund’s Adjuvant (CFA) into the hind paw, and treated with the IPA supplement. Behavioral assessments were conducted using the Von Frey test, cold or hot plate tests. The expression of pain-related transcripts, such as transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) was evaluated. Degree of inflammation was assessed by the thickness of paws, degree of inflammatory infiltration and the changes of serum tumor necrosis factor (TNF)-α, interleukin(IL)-6 and IL-1β.
Results: IPA supplement improved the CFA-induced decrease of the mechanical withdrawal threshold and cold and thermal withdrawal latency. Meanwhile, IPA inhibited the CFA-induced upregulation of TRPV1 and CGRP in DRGs. In addition, IPA treatment also suppressed the CFA-induced local and systemic inflammation, including the swelling and thickening of the paw, local infiltration of inflammatory cells, and increased serum levels of TNF-α, IL-6, and IL-1β.
Conclusion: Our results show that IPA can improve pain-related behavior and alleviate inflammation in the CFA–treated mice, which provides new insight into potential strategies for inflammatory pain management.

Keywords: indolepropionic acid, inflammatory pain, complete freund’s adjuvant, TRPV1, CGRP