Project Details
Description
Abstract
Neck and back pain have a tremendous annual incidence and associated costs. The facet capsular ligament
(FCL) encloses the bilateral articulating joints of the spinal vertebrae and is richly innervated to provide
proprioception during spinal motions. The FCL is also innervated by nociceptors and may act as a pain sensor
during abnormal conditions like injury and repeated loading. Although aberrant spinal motions and pathologic
conditions are associated with pain, the relationship between tissue loading and nociceptor activation is unclear
due to the complicated involvement of mechanics and physiology in the FCL across length scales. Accurately
relating spinal motions to neuronal function within the FCL requires multi-scale modeling and experiments to
identify the relevant mechanotransduction mechanisms by which tissue loading mediates neuronal function.
Under this U01 renewal, we will expand our prior work defining how the neuronal response is governed by
the forces from its local environment, which are determined by the complex interaction of macroscopic
loads and the microscopic structure of the FCL. We extend that work by improving our multiscale models of
FCL mechanics at the tissue, collagen fiber network, and neuronal scales. We will use those models to study
the mechanical environment of neurons in the tissue and its collagen matrix and to predict responses under
injury and pathologic conditions. Complementary experiments at the tissue and cell scales will characterize
neuron and matrix structure and architectural descriptions of neurons, as well as define rate effects and the
mechanical interactions between the FCL, collagen fibers, and neurons. We will integrate modeling and
experimental work under coordinated specific aims to define how the organization of fibrillar and non-fibrillar
material in the FCL govern its mechanical response to different loading scenarios, how the micro-scale fiber
motion translates into forces on neurons, and how those forces affect neuronal architecture, signaling and
function. In Aim 1, we will use advanced bioimaging, image-processing, and analytical tools to refine our existing
multiscale model and capture the complex geometry and architecture of the matrix and neurons in the FCL. In
Aim 2, we will define forces on the neurons during loading when its surrounding matrix deforms; Aim 3 includes
adding viscoelasticity and interstitial flow to our model and studying rate effects on both the tissue, matrix and
neurons. Finally, in Aim 4, we will insert our cellular/matrix model (µm-to-nm scale) into a whole-spine model
(mm-µm scale) to link realistic macroscopic loading to neuronal deformation in clinically relevant contexts. By
connecting the tissue and cellular scales, the project will facilitate efforts to include relevant physiological data
on joint mechanics during injury and clinically relevant-spinal conditions with afferent neuronal function, which
will promote understanding of the in vivo responses of the joints during pathologic motions and will not only
enhance our understanding of degeneration, arthritis, and injury in the FCL but also provide insight into other
innervated soft tissues with complex structure and geometry and speculative pain etiology.
Status | Finished |
---|---|
Effective start/end date | 8/15/18 → 7/31/23 |
Funding
- National Center for Complementary and Integrative Health: $656,995.00
- National Center for Complementary and Integrative Health: $657,130.00
- National Center for Complementary and Integrative Health: $690,076.00
- National Center for Complementary and Integrative Health: $46,498.00
- National Center for Complementary and Integrative Health: $656,995.00
- National Center for Complementary and Integrative Health: $663,279.00
- National Center for Complementary and Integrative Health: $34,341.00
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