High-velocity, low-amplitude spinal manipulation (HVLA-SM) is an efficacious treatment for low back pain, although the physiological mechanisms underlying its effects remain elusive. The lumbar facet joint capsule (FJC) is innervated with mechanically sensitive neurons and it has been theorized that the neurophysiological benefits of HVLA-SM are partially induced by stimulation of FJC neurons. Biomechanical aspects of this theory have been investigated in humans while neurophysiological aspects have been investigated using cat models. The purpose of this study was to determine the relationship between human and cat lumbar spines during HVLA-SM. Cat lumbar spine specimens were mechanically tested, using a displacement-controlled apparatus, during simulated HVLA-SM applied at L5, L6, and L7 that produced preload forces of approximately 25% bodyweight for 0.5 s and peak forces that rose to 50-100% bodyweight within approximately 125 ms, similar to that delivered clinically. Joint kinematics and FJC strain were measured optically. Human FJC strain and kinematics data were taken from a prior study. Regression models were established for FJC strain magnitudes as functions of factors species, manipulation site, and interactions thereof. During simulated HVLA-SM, joint kinematics in cat spines were greater in magnitude compared with humans. Similar to human spines, site-specific HVLA-SM produced regional cat FJC strains at distant motion segments. Joint motions and FJC strain magnitudes for cat spines were larger than those for human spine specimens. Regression relationships demonstrated that species, HVLA-SM site, and interactions thereof were significantly and moderately well correlated for HVLA-SM that generated tensile strain in the FJC. The relationships established in the current study can be used in future neurophysiological studies conducted in cats to extrapolate how human FJC afferents might respond to HVLA-SM. The data from the current study warrant further investigation into the clinical relevance of site targeted HVLA-SM.
"Additionally, by using flexible silicone rubber dishes this culture device can apply low-frequency cyclic strain to modulate mesenchymal stem cell and C2C12 myoblast cell differentiation [13,14]. We also demonstrated that this device can apply high-magnitude near-injurious strain [15,16] to intervertebral disc (IVD) cells  resulting in increased NGF, TNF and inflammatory factor expression which may be related to low back pain. It is generally accepted that OA progression causes lower tissue compressive properties, resulting in higher tensile strains to resident cells—a process that can directly affect cell phenotype, metabolism and viability. "
[Show abstract][Hide abstract] ABSTRACT: Osteoarthritis (OA) is a debilitating joint disorder resulting from an incompletely understood combination of mechanical, biological, and biochemical processes. OA is often accompanied by inflammation and pain, whereby cytokines associated with chronic OA can up-regulate expression of neurotrophic factors such as nerve growth factor (NGF). Several studies suggest a role for cytokines and NGF in OA pain, however the effects of changing mechanical properties in OA tissue on chondrocyte metabolism remain unclear. Here, we used high-extension silicone rubber membranes to examine if high mechanical strain (HMS) of primary articular chondrocytes increases inflammatory gene expression and promotes neurotrophic factor release. HMS cultured chondrocytes displayed up-regulated NGF, TNFα and ADAMTS4 gene expression while decreasing TLR2 expression, as compared to static controls. HMS culture increased p38 MAPK activity compared to static controls. Conditioned medium from HMS dynamic cultures, but not static cultures, induced significant neurite sprouting in PC12 cells. The increased neurite sprouting was accompanied by consistent increases in PC12 cell death. Low-frequency high-magnitude mechanical strain of primary articular chondrocytes in vitro drives factor secretion associated with degenerative joint disease and joint pain. This study provides evidence for a direct link between cellular strain, secretory factors, neo-innervation, and pain in OA pathology.
International Journal of Molecular Sciences 08/2014; 15(8). DOI:10.3390/ijms150814427 · 2.86 Impact Factor
"Additionally, we have shown that low-frequency, high-magnitude cyclical strain applied by this device can modulate stem cell differentiation and lineage specification [18,19]. Because the culture surface can be expanded to magnitudes approaching injurious strain [20,21]. We hypothesized that high-amplitude cyclical mechanical strain (20% at a low frequency of 0.001 Hz) of AF and nucleus pulposus (NP) cells can directly promote inflammatory factor secretion associated with spinal disc degeneration, innervation and pain. "
[Show abstract][Hide abstract] ABSTRACT: Excessive mechanical loading of intervertebral discs (IVD) is thought to alter matrix properties and influence disc cell metabolism, contributing to degenerative disc disease and development of discogenic pain. However, little is known about how mechanical strain induces these changes. This study investigated the cellular and molecular changes as well as which inflammatory receptors and cytokines were up-regulated in human intervertebral disc cells exposed to high mechanical strain (HMS) at low frequency. The impact of these metabolic changes on neuronal differentiation was also explored to determine a role in the development of disc degeneration and discogenic pain.
Isolated human annulus fibrosus (AF) and nucleus pulposus (NP) cells were exposed to HMS (20% cyclical stretch at 0.001 Hz) on high-extension silicone rubber dishes coupled to a mechanical stretching apparatus and compared to static control cultures. Gene expression of toll-like receptors (TLR), neuronal growth factor (NGF) and tumor necrosis factor alpha (TNFalpha) was assessed. Collected conditioned media was analyzed for cytokine content and applied to rat pheocromocytoma PC12 cells for neuronal differentiation assessment.
HMS caused up-regulation of TLR2, TLR4, NGF and TNFalpha gene expression in IVD cells. Medium from HMS cultures contained elevated levels of growth related oncogene, interleukin (IL)-6, IL-8, IL-15, monocyte chemoattractant protein (MCP)-1, MCP-3, monokine induced by gamma interferon, transforming growth factor beta-1, TNFalpha and NGF. Exposure of PC12 cells to HMS-conditioned media resulted in both increased neurite sprouting and cell death.
HMS culture of IVD cells in vitro drives cytokine and inflammatory responses associated with degenerative disc disease and low back pain. This study provides evidence for a direct link between cellular strain, secretory factors, neo-innervation and potential degeneration and discogenic pain in vivo.
[Show abstract][Hide abstract] ABSTRACT: Today, it is easy to provide information to and retrieve
information from the Internet. However, the problem of information
overload has to be overcome. One of the main issues to be addressed for
the information overload problem is document classification. We present
an evolutionary approach to automatically categorize documents into
appropriate categories. Our approach deals with different categories of
documents separately: it evolves a numerical list that consists of the
corresponding weights of the feature words for each class of documents.
Experimental results show that our approach can easily evolve the
classifiers of numerical lists, and that the evolved classifiers perform
better than those constructed by the traditional k-nearest neighbors
Systems, Man, and Cybernetics, 2000 IEEE International Conference on; 02/2000
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