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The contributions of neural control and mechanosensation to rehabilitation induced spine muscle recovery

Award Number: R01HD088437
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2017
PERIOD OF PERFORMANCE END DATE: 04/30/2030

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The contributions of neural control and mechanosensation to rehabilitation induced spine muscle recovery - PROJECT SUMMARY Low back pain (LBP) is a complex condition that affects 65-85% of the population, and is the leading musculoskeletal condition contributing to disability in the United States. Disc injury is the most common injury and 75% of individuals undergoing surgical and rehabilitative interventions for this condition experience suboptimal or poor outcomes. These patients demonstrate disability and deficits in functional capacity, and paraspinal muscles in these individuals have been shown to be altered in volume, composition, and mechanical properties. These maladaptive changes influence the ability for the muscle to respond appropriately to rehabilitation efforts in a subgroup of individuals with chronic back pain who do not demonstrate the expected acute activation responses to exercise. While the structural and adaptive capacities of healthy muscle are well understood, pathological muscle recovery and activation deficits are less clear and may be influenced by neurogenic and/or muscle specific impairments. To address this gap in knowledge, the purpose of this proposal is to compare central and peripheral origins of impaired activation in individuals with chronic disc injury who do, and do not respond to exercise. Our central hypothesis is that individuals with non-responsive chronic disc injury will demonstrate a spectrum of impairments in cortical activation, peripheral nerve physiology, and/or muscle dysfunction that preclude normal responses to exercise. Aim 1 will use a novel functional MRI technique and electromyographic measurements to compare responder and non-responder groups in patients with chronic lumbar disc injury. Aim 2 will compare corticomotor excitability and intracortical inhibition and facilitation between individuals who do and do not respond to exercise. Aim 3 will compare ex vivo passive and active mechanical responses, and transcriptomics from intraoperative multifidus biopsies of patients with chronic lumbar disc injury to evaluate muscle mechanotransduction. These experiments will elucidate the neurogenic and muscle-specific contributions to muscle adaptation in the presence of chronic lumbar spine pathology and pain. These contributions are significant because they are critical steps in a precision medicine approach aimed at reversing maladaptive muscle changes that obstruct patient recovery. The proposal is innovative because it combines novel direct tissue testing, cortical assessments, and spine imaging methods to measure muscle structure, function, and adaptation in living humans. We expect an immediate impact on rehabilitation because these findings will provide data and methods for identifying patients who will, or will not, respond to standard rehabilitation programs. In the long-term, we expect these experiments to provide direction for unique, patient-specific pharmacological, surgical and rehabilitation programs.


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: 2026 ( Subtotal = $682,183 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Child Health and Human Development Extramural Research	000	7	5/4/2026	NON-COMPETING CONTINUATION	$682,183
														Subtotal = $682,183

Issue Date FY: 2025 ( Subtotal = $675,801 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Child Health and Human Development Extramural Research	000	6	5/2/2025	COMPETING CONTINUATION	$675,801
														Subtotal = $675,801

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Child Health and Human Development Extramural Research	000	5	12/15/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $298,703 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Child Health and Human Development Extramural Research	000	5	3/30/2021	NON-COMPETING CONTINUATION	$298,703
														Subtotal = $298,703

Issue Date FY: 2020 ( Subtotal = $306,328 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Child Health and Human Development Extramural Research	000	4	4/7/2020	NON-COMPETING CONTINUATION	$306,328
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Child Health and Human Development Extramural Research	001	4	7/13/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $306,328

Issue Date FY: 2019 ( Subtotal = $307,719 )
2019	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Child Health and Human Development Extramural Research	000	3	3/19/2019	NON-COMPETING CONTINUATION	$307,719
														Subtotal = $307,719

Issue Date FY: 2018 ( Subtotal = $308,983 )
2018	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Child Health and Human Development Extramural Research	001	2	5/1/2018	NON-COMPETING CONTINUATION	$30,899
2018	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Child Health and Human Development Extramural Research	000	2	3/22/2018	NON-COMPETING CONTINUATION	$278,084
														Subtotal = $308,983

Issue Date FY: 2017 ( Subtotal = $310,133 )
2017	2017	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Child Health and Human Development Extramural Research	000	1	6/30/2017	NEW	$310,133
														Subtotal = $310,133

Grand Total All Awards = $2,889,850

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The contributions of neural control and mechanosensation to rehabilitation induced spine muscle recovery

Award Number: R01HD088437

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2017

PERIOD OF PERFORMANCE END DATE: 04/30/2030

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