Ao Rui-Feng, Yong Heng-Rui, Hu Ying-Tao, Huang Yu-Sheng, Gao Jia-Wen, Tu Chen, Zhuang Jing-Shen, Zhong Zhao-Ming
Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Department of Orthopedics, Academy of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People's Republic of China.
J Pain Res. 2025 May 23;18:2643-2650. doi: 10.2147/JPR.S525859. eCollection 2025.
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.
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.
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.
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.
慢性疼痛是一个全球性的健康问题，影响着多达20%的人口。炎症性疼痛是慢性疼痛的一种重要形式，对患者的生活质量产生负面影响。吲哚丙酸（IPA）是一种源自肠道微生物群的代谢产物，具有抗炎特性。然而，其对炎症性疼痛的影响尚未得到研究。本研究旨在探讨IPA对弗氏完全佐剂（CFA）诱导的炎症性疼痛的影响。
通过将弗氏完全佐剂（CFA）注射到后爪建立炎症性疼痛小鼠模型，并用IPA补充剂进行治疗。使用von Frey试验、冷板或热板试验进行行为评估。评估疼痛相关转录本的表达，如瞬时受体电位香草酸受体1（TRPV1）和降钙素基因相关肽（CGRP）。通过爪的厚度、炎症浸润程度以及血清肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6和IL-1β的变化来评估炎症程度。
补充IPA改善了CFA诱导的机械性退缩阈值降低以及冷、热退缩潜伏期缩短。同时，IPA抑制了CFA诱导的背根神经节中TRPV1和CGRP的上调。此外，IPA治疗还抑制了CFA诱导的局部和全身炎症，包括爪的肿胀和增厚、炎症细胞的局部浸润以及血清TNF-α、IL-6和IL-1β水平的升高。
我们的结果表明，IPA可以改善CFA处理小鼠的疼痛相关行为并减轻炎症，这为炎症性疼痛管理的潜在策略提供了新的见解。
