Persistent pain signaling and stress response in a mouse model of inflammatory low back pain

Abstract

Introduction: Chronic low back pain (LBP) is linked to dysfunction in both peripheral and central nervous systems and is a risk factor of psychiatric disorders such as depression. However, pain-related signaling in sensory and central neurons during chronic LBP, and its impact on stress-induced emotional behaviors, remains poorly understood.

Objectives: The aim of this study was to investigate persistent changes in pain-related and inflammation-related signaling in an inflammatory LBP mouse model and assess its influence on stress-related behaviors.

Methods: An LBP-like condition was induced by administering complete Freund adjuvant to the lumbar region in mice. Behavioral assessments included gait analysis and mechanical sensitivity testing. Gene expression and immunohistological changes in the dorsal root ganglia (DRG), spinal cord, and brain regions were examined. Chronic social defeat stress (CSDS) was used to evaluate stress susceptibility and emotion-related behavior.

Results: Complete Freund adjuvant-induced lumbar inflammation led to delayed onset of LBP-like behaviors, including impaired gait and hindpaw hypersensitivity, persisting into the chronic phase. Expression of inflammatory and pain-related genes was significantly elevated in the DRG and spinal cord in the lumbar region. Increased microglial activation and reduced Bdnf expression in the hippocampus were observed, accompanied by impaired hippocampal neurogenic process. Mice with LBP-like conditions exhibited heightened avoidance behavior following CSDS and an exaggerated hippocampal stress response.

Conclusion: Chronic inflammation-induced LBP disrupts both peripheral and central neural function and may contribute to increased stress susceptibility and depression-like behaviors.

Keywords: Avoidance behavior; Hippocampus; Inflammation; Low back pain; Microglia; Muscle; Neurogenesis; Sensory neuron; Social defeat stress; Spinal cord.