Motohashi Hiroaki, Yamaji Yasuhito, Mori Kazunari, Washizu Sena, Hoshino Oki, Fujimoto Kotone, Kanazawa Seiji, Minegishi Yoshihiko, Ota Noriyasu, Mori Takuya, Segi-Nishida Eri
Kao Corporation, Ichikai-machi, Haga-gun, Tochigi, Japan.
Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, Japan.
Pain Rep. 2025 Jun 25;10(4):e1300. doi: 10.1097/PR9.0000000000001300. eCollection 2025 Aug.
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.
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.
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.
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 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.
Chronic inflammation-induced LBP disrupts both peripheral and central neural function and may contribute to increased stress susceptibility and depression-like behaviors.
慢性下腰痛（LBP）与外周和中枢神经系统功能障碍有关，是抑郁症等精神疾病的危险因素。然而，慢性LBP期间感觉神经元和中枢神经元中与疼痛相关的信号传导及其对压力诱导的情绪行为的影响仍知之甚少。
本研究旨在调查炎症性LBP小鼠模型中与疼痛相关和炎症相关信号的持续变化，并评估其对压力相关行为的影响。
通过向小鼠腰椎区域注射完全弗氏佐剂诱导类似LBP的病症。行为评估包括步态分析和机械敏感性测试。检查背根神经节（DRG）、脊髓和脑区的基因表达和免疫组织学变化。使用慢性社会挫败应激（CSDS）评估压力易感性和情绪相关行为。
完全弗氏佐剂诱导的腰部炎症导致类似LBP行为的延迟发作，包括步态受损和后爪超敏反应，持续到慢性期。腰部DRG和脊髓中炎症和疼痛相关基因的表达显著升高。观察到海马中小胶质细胞激活增加和表达减少，同时伴有海马神经发生过程受损。患有类似LBP病症的小鼠在CSDS后表现出增强的回避行为和夸张的海马应激反应。
慢性炎症诱导的LBP会破坏外周和中枢神经功能，并可能导致压力易感性增加和类似抑郁的行为。
