The progression of infiltrating neurovascular features and chemokine production of the caudal intervertebral disc following injury.

The accessibility of the mouse caudal intervertebral disc (IVD) and its geometric semblance to the human IVD makes it an attractive model for assessing IVD-specific responses in vivo . To effectively utilize this model, the temporal trajectories of key pathoanatomical features, such as the production of inflammatory chemokines, tissue disorganization, and neo- vessel and neurite infiltration, must be understood. This study aims to define the progression of chemokine production and neurovascular invasion at 2-, 4-, and 12-weeks following a caudal IVD injury in 3-month-old female C57BL6/J mice. We measured IVD-secreted chemokines and matrix metalloproteinases (MMPs) using multiplex ELISA, graded the histopathological degeneration, and quantified the intradiscal infiltrating vessels (endomucin) and nerves (protein-gene-product 9.5) using immunohistochemistry. Injury provoked the secretion of IL6, CCL2, CCL12, CCL17, CCL20, CCL21, CCL22, CXCL2 and MMP2 proteins. Neurites propagated rapidly within 2-weeks post-injury and remained relatively constant until 12-weeks. Peak vascular vessel length occurred at 4-weeks post-injury and regressed by 12-weeks. These findings identified the temporal flux of inflammatory chemokines and pain-associated pathoanatomy in a model of IVD degeneration using the mouse caudal spine.