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Mechanistic structure-function relationships for paraspinal muscle fat infiltration in chronic low back pain patients

Award Number: R01AR081324
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Mechanistic structure-function relationships for paraspinal muscle fat infiltration in chronic low back pain patients - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $319,770 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	3/20/2025	NON-COMPETING CONTINUATION	$319,770
														Subtotal = $319,770

Issue Date FY: 2024 ( Subtotal = $344,641 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	2	6/11/2024	NON-COMPETING CONTINUATION	$24,871
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	3/25/2024	NON-COMPETING CONTINUATION	$319,770
2024	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	1/5/2024	NEW	$0
														Subtotal = $344,641

Issue Date FY: 2023 ( Subtotal = $355,300 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	5/24/2023	NEW	$355,300
														Subtotal = $355,300

Grand Total All Awards = $1,019,711

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Mechanistic structure-function relationships for paraspinal muscle fat infiltration in chronic low back pain patients

Award Number: R01AR081324

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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