Abstract
BACKGROUND CONTEXT
Endplate (EP) injury plays critical roles in painful IVD degeneration since Modic
changes (MCs) are highly associated with pain. Models of EP microfracture that progress
to painful conditions are needed to better understand pathophysiological mechanisms
and screen therapeutics.
PURPOSE
Establish in vivo rat lumbar EP microfracture model and assess crosstalk between IVD,
vertebra and spinal cord.
STUDY DESIGN/SETTING
In vivo rat EP microfracture injury model with characterization of IVD degeneration,
vertebral remodeling, spinal cord substance P (SubP), and pain-related behaviors.
METHODS
EP-injury was induced in 5 month-old male Sprague-Dawley rats L4–5 and L5–6 IVDs by
puncturing through the cephalad vertebral body and EP into the NP of the IVDs followed
by intradiscal injections of TNFα (n=7) or PBS (n=6), compared with Sham (surgery
without EP-injury, n=6). The EP-injury model was assessed for IVD height, histological
degeneration, pain-like behaviors (hindpaw von Frey and forepaw grip test), lumbar
spine MRI and μCT, and spinal cord SubP.
RESULTS
Surgically-induced EP microfracture with PBS and TNFα injection induced IVD degeneration
with decreased IVD height and MRI T2 signal, vertebral remodeling, and secondary damage
to cartilage EP adjacent to the injury. Both EP injury groups showed MC-like changes
around defects with hypointensity on T1-weighted and hyperintensity on T2-weighted
MRI, suggestive of MC type 1. EP injuries caused significantly decreased paw withdrawal
threshold, reduced axial grip, and increased spinal cord SubP, suggesting axial spinal
discomfort and mechanical hypersensitivity and with spinal cord sensitization.
CONCLUSIONS
Surgically-induced EP microfracture can cause crosstalk between IVD, vertebra, and
spinal cord with chronic pain-like conditions.
CLINICAL SIGNIFICANCE
This rat EP microfracture model was validated to induce broad spinal degenerative
changes that may be useful to improve understanding of MC-like changes and for therapeutic
screening.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: April 20, 2023
Accepted:
April 18,
2023
Received in revised form:
April 5,
2023
Received:
November 17,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
FDA device/drug status: Not applicable.
Author disclosures: DW: Nothing to disclose. AL: Grant: NIH/NIAMS (Paid directly to institution). JG: Grant: NIH/NIAMS (Paid directly to institution). ACS: Grant: NIH/NIAMS (Paid directly to institution). JM: Grant: NIH/NIAMS (Paid directly to institution). KZ: NIH/NIAMS (Paid directly to institution). NB: NIH/NIAMS (Paid directly to institution). YL: NIH/NIAMS (Paid directly to institution). PN: NIH/NIAMS (Paid directly to institution). DML: NIH/NIAMS (Paid directly to institution). NH: NIH/NIAMS (G, Paid directly to institution). ACH: NIH/NIAMS (G, Paid directly to institution). JCL: (G, Paid directly to institution).
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