Genetics- and age-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated...

Area of Science:

• Biomedical Science
• Genetics
• Immunology

Background:

• Lack of suitable wild-type mouse models for studying spontaneous disc herniation pathophysiology.
• SM/J mice, known for poor healing, exhibit a high incidence of age-associated lumbar disc herniations with neurovascularization.

Purpose of the Study:

• To characterize a novel murine model (SM/J mice) for spontaneous disc herniation.
• To investigate the underlying mechanisms, including genetic and aging contributions, and associated immune responses.

Main Methods:

• Utilized SM/J mice to study spontaneous disc herniation.
• Performed transcriptomic analysis of annulus fibrosus and compared with human tissues.
• Conducted cytometry by time-of-flight and single-cell RNA sequencing on various tissues and blood cells.
• Assessed pain sensitization and neuroinflammation in aged mice.

Main Results:

• SM/J mice showed high incidence of age-associated lumbar disc herniations with neurovascular innervations.
• Transcriptomic data revealed shared inflammatory and immune cell activation pathways between SM/J mice and human tissues.
• Aged SM/J mice exhibited increased pain sensitization, neuroinflammation, and altered extracellular matrix regulation.
• Elevated T cells in vertebral marrow, increased splenic CD8+ T cells, and enhanced interferon-γ production were observed.
• Peripheral blood analysis indicated alterations in B cells, T cells, monocytes, and granulocytes.

Conclusions:

• SM/J mice represent a clinically relevant model for spontaneous intervertebral disc herniation.
• Genetic background and aging significantly contribute to susceptibility to disc herniation.
• The study implicates immune system activation and inflammation in the pathophysiology of disc herniation.