37: The mechanism of VTA neurons in alleviating low back pain caused by bone endplate cavities

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Neuroimmunology

Background and Aims: Low back pain is one of the most common clinical symptoms in orthopedics. It not only severely impairs patients' physical and mental health and reduces their quality of life but also imposes a substantial social burden and economic loss. Intervertebral disc degeneration is a major cause of chronic low back pain. Patients with chronic low back pain may present with structural or functional alterations in specific regions of the central nervous system; however, their clinical significance has yet to be fully elucidated.

Methods: This study investigated sympathetic regulation of lumbar endplate cavitation in low back pain using a mouse lumbar spine instability model. Approaches included PRV retrograde tracing, pharmacological inhibition, conditional knockout of ADRB2, RNA-seq, and DREADD manipulation of VTA-DA neurons. Outcomes assessed sympathetic tone, osteoclastogenesis, sensory innervation, pain behaviors, and neuronal excitability to elucidate the neuroanatomical and molecular mechanisms underlying discogenic pain.

Results: Moderate activation of VTA-DA neurons can downregulate sympathetic nerve tension in the lumbar vertebral endplate, and remodel the osteoblast-osteoclast functional balance within endplate cavities by confining the expression of ADRB2 in osteoclasts. The appropriate response of sympathetic tone in osteoclasts promote cavity healing, and alleviate symptoms of discogenic low back pain.

Conclusions: This project intends to elucidate a novel "brain-bone axis" neural pathway, clarify the effect of specifically activating VTA-DA neurons in alleviating low back pain caused by vertebral endplate cavities, and deeply reveal the regulatory mechanisms involving sympathetic nerve tension and osteoblast-osteoclast homeostasis.

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Presenting Author: Haiyue Zhao
Submitting Author: Haiyue Zhao

Senior Author: Shuiqing Li

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Haiyue Zhao - Peking University the Third Hospital
• Shengyu Cui - Peking University the Third Hospital
• Yuanren Zhai - Peking University the Third Hospital
• Qipeng Luo - Peking University the Third Hospital
• Shuiqing Li - Peking University the Third Hospital