PROJECT SUMMARY
Chronic low back pain (cLBP) is the world's leading debilitating condition and the most common reason for
opioid prescription in the US. While axial cLBP is commonly considered non-specific and multifactorial, it is
often suspected a dysfunction of the spinal stabilization system that includes the intervertebral disc (IVD) and
adjacent paraspinal muscles (PSMs). Axial cLBP is notoriously challenging to treat because of uncertainty
about patient-specific causal mechanisms preventing effective matching to treatments. IVD degeneration is
easily appreciated with clinical imaging and often studied. Less is known about the role of PSM degeneration,
including atrophy and fat infiltration (FI), which are assumed to relate to cLBP, although existing evidence does
not provide a clear association. Given the availability of advanced MRI sequences that quantify FI, it is now
possible to investigate PSM FI patterns that will inform how it may relate to functional outcomes in cLBP
patients.
The current working hypothesis is that degenerative IVD pathology promotes PSM FI as a result of a
compensatory biomechanical response of the muscle in an attempt to stabilize an affected spinal segment that
overtime leads to neuromuscular fatigue and/or from direct exposure to pro-inflammatory factors from IVD
damage. We hypothesize that PSM FI spatial distribution patterns (fat maps) have significant correlation with 1)
patient-specific kinematics and PSM activation patterns (i.e. motor control), and 2) bimolecular factors, derived
from patient PSM muscle biopsy. To test this hypothesis, we will quantify PSM FI, degenerative IVD pathology,
trunk and full-body kinematics, and paraspinal muscle activation in 40 axial cLBP subjects and 40 age-matched
controls. We will also collect a muscle tissue sample from the cLBP patients to uncover the biomolecular
mechanisms of PSM FI. In this study, we are proposing to 1) quantify spatial distribution of paraspinal muscle
fat infiltration and associate resulting fat maps with cLBP and degenerative IVD pathology, 2) quantify motor
control patterns from multi-domain muscle activation and kinematics data types and associate with cLBP
symptoms and PSM FI, and 3) uncover different potential biomolecular mechanisms underlying distinct PSM FI
and motor control patterns in cLBP patients. This study has been uniquely crafted to investigate different reasons
for how PSM might become infiltrated with fat in axial cLBP patients and, furthermore, the potentially disabling
functional outcomes associated with PSM FI in cLBP patients. This work will advance our understanding of the
clinical relevance and causal mechanisms of PSM FI in relation to cLBP and inform future efforts to use PSM
FI as an imaging biomarker to optimize patient-selection for specific muscle-targeting cLBP therapies to
improve outcomes.
