This study aims to understand the connection between chronic low back pain, stress, and depression by developing a mouse model. To develop a low back pain model in mice, Complete Freund's Adjuvant (CFA) was administered to the muscle around lumbar region. To evaluate locomotion and balance ability, the balance beam test was performed. Goal-reaching time was increased from day 14 to day 28 in the CFA-treated group, indicating a long-term decline in locomotor performance. To examine the central influence of low back pain model in the hippocampus, we examined the expression of microglia marker Iba1 and neuorogenic marker NeuroD1 in the dentate gryus (DG) of hippocampus 28 days after CFA administration. Iba1-positive cells were increased, and NeuroD1-positive cells were decreased in the DG of the CFA-treated group, indicating long lasting influence of low back inflammation on the hippocampus. Next, we evaluated the influence of the low back pain model on the responses to chronic stress. Mice were exposed to 10 days of social defeat stress before CFA treatment. Although social avoidance behavior was observed shortly after stress, it dissipated 38 days later in the stress alone group. In contrast, social avoidance behavior was more pronounced in CFA-treated mice than in mice exposed to stress alone. These results demonstrate that CFA-induced low back pain model showed long lasting locomotion and balance inability, histological changes in the hippocampus, and exacerbating the stress response. The developed model in this study can aid in elucidating the neuronal mechanism of low back pain and understanding how low back pain intensifies stress.
