Abstract
Background: Pyrroloquinoline Quinone (PQQ) is a redox cofactor with potent antioxidant and anti-inflammatory properties. This study investigated the therapeutic potential of PQQ in alleviating spinal pain and degeneration in a lumbar spine instability (LSI) mouse model. LSI is commonly associated with spinal pain and structural degeneration, with senescent osteoclasts (SnOCs) involved in spinal hypersensitivity and degeneration. Methods: LSI was induced in 8-week-old C57/BL6 mice by surgically resecting the L3–L5 spinous processes and associated ligaments. The mice were treated with PQQ, and behavioral tests (spinal hypersensitivity, anxiety, and activity levels) were conducted. Spinal endplate structural integrity was assessed through micro-computed tomography imaging and histological analyses. Immunohistochemical staining was performed to identify SnOCs and inflammatory markers. Results: PQQ treatment significantly reduced pain-related hypersensitivity and anxiety behaviors in LSI mice. Behavioral improvements were demonstrated by increased activity, quicker heat response times, and reduced mechanical hypersensitivity. PQQ treatment also preserved the microarchitecture of spinal endplates by reducing endplate porosity, trabecular separation, and osteoclast activity. Additionally, PQQ reduced the number of SnOCs and modulated their inflammatory secretory phenotype, thereby decreasing sensory nerve innervation and angiogenesis in the spinal endplates. Conclusions: PQQ alleviates spinal pain and degeneration by targeting SnOCs, modulating inflammation, and preserving spinal microarchitecture. These findings suggest that PQQ has potential as a therapeutic agent for managing pain and structural degeneration in spinal instability-related disorders. Supplementary Information: The online version contains supplementary material available at 10.1186/s12967-025-07212-9.