Lee Elmo Wing-Yiu, Wang Lin, Liu Jessica Ai-Jia, Cheung Chi-Wai
Department of Anaesthesiology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Department of Neuroscience, City University of Hong Kong, Hong Kong SAR, China.
Int J Mol Sci. 2025 Jun 5;26(11):5422. doi: 10.3390/ijms26115422.
Chronic inflammatory pain (IP) remains a therapeutic challenge under the worldwide prevalence of the high-fat dietary lifestyle. This study aimed at identifying mediators of the IP augmented by short-term high-fat diet (HFD). IP was induced on C57BL/6J mice by unilateral, intra-plantar, injection of Complete Freund's Adjuvant (CFA). Von Frey test for mechanical hyperalgesia and Hargreaves' test for thermal hyperalgesia were performed at pre-injection baseline and post-injection 6th h. and days 1/3/5/7/10/14. Ad libitum HFD feeding started 2 weeks pre-injection in assigned groups. Body weight and random blood glucose levels were measured. RT-qPCR and ELISA helped quantify expression levels of the selected candidate genes at manipulated hind-paws. After CFA injection, at 1400 W, a highly selective inducible nitric oxide synthase () inhibitor was administered regularly to elicit differences in CFA-induced pain behaviors and gene expression in HFD-fed mice. Results showed that HFD-fed mice were heavier ( < 0.001) and relatively hyperglycemic ( = 0.013) at baseline. HFD aggravated CFA-induced mechanical and thermal pain (mechanical: = 0.0004, thermal: = 0.003), showing prolonged hyperalgesic durations and reduced pain thresholds at multiple timepoints. HFD-influenced paws showed accentuated overexpression of pro-inflammatory cytokines and (RT-qPCR for : = 0.015, : = 0.019, : = 0.04; ELISA for : = 0.011). At 1400 W, exertion of analgesic effects (mechanical: < 0.0001, thermal: < 0.0001) but pro-inflammatory (RT-qPCR for : = 0.004, : = 0.03, : = 0.04) were exerted on the inflamed paw on day 5 post-injection. In conclusion, short-term HFD aggravated CFA-induced inflammatory pain. Pharmacological inhibition of attenuated the CFA-induced pain in HFD-fed mice. Future research might uncover signaling pathways mediating such effects, potentially benefiting obese patients with chronic IP.
在高脂肪饮食生活方式全球流行的背景下，慢性炎症性疼痛（IP）仍然是一个治疗难题。本研究旨在确定短期高脂肪饮食（HFD）加剧的IP的介质。通过单侧足底注射完全弗氏佐剂（CFA）在C57BL/6J小鼠上诱导IP。在注射前基线以及注射后第6小时和第1、3、5、7、10、14天进行机械性痛觉过敏的von Frey试验和热痛觉过敏的哈格里夫斯试验。在指定组中，在注射前2周开始随意给予HFD喂养。测量体重和随机血糖水平。RT-qPCR和ELISA有助于定量所选择的候选基因在被处理后爪中的表达水平。在CFA注射后，在第1400W时，定期给予一种高度选择性的诱导型一氧化氮合酶（）抑制剂，以引发HFD喂养小鼠中CFA诱导的疼痛行为和基因表达的差异。结果显示，在基线时，HFD喂养的小鼠更重（<0.001）且相对血糖较高（=0.013）。HFD加剧了CFA诱导的机械性和热痛（机械性：=0.0004，热痛：=0.003），在多个时间点显示出痛觉过敏持续时间延长和疼痛阈值降低。受HFD影响的爪子显示促炎细胞因子和的表达明显上调（的RT-qPCR：=0.015，：=0.019，：=0.04；的ELISA：=0.011）。在第1400W时，在注射后第5天对发炎的爪子发挥了镇痛作用（机械性：<0.0001，热痛：<0.0001），但也有促炎作用（的RT-qPCR：=0.004，：=0.03，：=0.04）。总之，短期HFD加剧了CFA诱导的炎症性疼痛。对的药理学抑制减轻了HFD喂养小鼠中CFA诱导的疼痛。未来的研究可能会揭示介导这种作用的信号通路，这可能使患有慢性IP的肥胖患者受益。
