AUTHOR=Pan Yushuang , Hu Qimiao , Yang Yunqin , Nie Huimin , Yin Chengyu , Wei Huina , Tai Yan , Liu Boyu , Shen Zui , He Xiaofen , Fang Jianqiao , Liu Boyi 

TITLE=Characterization of pain-related behaviors and gene expression profiling of peripheral sensory ganglia in a mouse model of acute ankle sprain

JOURNAL=Frontiers in Behavioral Neuroscience

VOLUME=Volume 17 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2023.1189489

DOI=10.3389/fnbeh.2023.1189489

ISSN=1662-5153

ABSTRACT=Lateral ankle sprain is a very common type of joint injury. It occurred with high incidence among general population and especially among individuals participating sports and outdoor activities. A certain proportion of individuals who once developed LAS may suffer persistent ankle pain that affects daily activities. However, the mechanisms underlying LAS-induced pain still remained largely unknown. Here, we first established a LAS mouse model and systematically evaluated the pain-related behaviors in this mouse model. The LAS model mice developed obvious signs of mechanical and heat hypersensitivities as well as gait impairments in ipsilateral hind paws. Besides, LAS model mice developed signs of pain-related emotional disorder, including pain-induced aversion. By RNA-Seq, we were able to identify certain differentially expressed genes and signaling pathways that might contribute to pain mechanisms of LAS mouse model. In addition, LAS model mice showed increased c-Fos and p-ERK immunoreactivity as well as astrocyte and microglia cell overactivation in ipsilateral spinal cord dorsal horn, indicating central sensitization might occur. Finally, LAS model mice respond to ibuprofen, a drug clinically used to treat ankle sprain pain. Therefore, we demonstrate that LAS model mice showed persistent pain-related behavior that responds to clinically active drugs and may, therefore, be used as a preclinical animal model for screening novel targets or therapies for ankle sprain. Our study may further help to understand molecular mechanisms contributing to ankle sprain-induced pain.