James R. Fox

Evidence of connective tissue involvement in acupuncture

Acupuncture needle manipulation gives rise to “needle grasp,” a biomechanical phenomenon characterized by an increase in the force necessary to pull the needle out of the tissue (pullout force). This study investigates the hypothesis that winding of connective tissue, rather than muscle contraction, is the mechanism responsible for needle grasp. We performed 1) measurements of pullout force in humans with and without needle penetration of muscle; 2) measurements of pullout force in anesthetized rats, with and without needle rotation, followed by measurements of connective tissue volume surrounding the needle; 3) imaging of rat abdominal wall explants, with and without needle rotation, using ultrasound scanning acoustic microscopy. We found 1) no evidence that increased penetration of muscle results in greater pullout force than increased penetration of subcutaneous tissue; 2) that both pullout force and subcutaneous tissue volume were increased by needle rotation; 3) that increased periodic architectural order was present in subcutaneous tissue with rotation, compared with no rotation. These data support connective tissue winding as the mechanism responsible for the increase in pullout force induced by needle rotation. Winding may allow needle movements to deliver a mechanical signal into the tissue and may be key to acupunctures therapeutic mechanism.

Reduced thoracolumbar fascia shear strain in human chronic low back pain

BackgroundThe role played by the thoracolumbar fascia in chronic low back pain (LBP) is poorly understood. The thoracolumbar fascia is composed of dense connective tissue layers separated by layers of loose connective tissue that normally allow the dense layers to glide past one another during trunk motion. The goal of this study was to quantify shear plane motion within the thoracolumbar fascia using ultrasound elasticity imaging in human subjects with and without chronic low back pain (LBP).MethodsWe tested 121 human subjects, 50 without LBP and 71 with LBP of greater than 12 months duration. In each subject, an ultrasound cine-recording was acquired on the right and left sides of the back during passive trunk flexion using a motorized articulated table with the hinge point of the table at L4-5 and the ultrasound probe located longitudinally 2 cm lateral to the midline at the level of the L2-3 interspace. Tissue displacement within the thoracolumbar fascia was calculated using cross correlation techniques and shear strain was derived from this displacement data. Additional measures included standard range of motion and physical performance evaluations as well as ultrasound measurement of perimuscular connective tissue thickness and echogenicity.ResultsThoracolumbar fascia shear strain was reduced in the LBP group compared with the No-LBP group (56.4% ± 3.1% vs. 70.2% ± 3.6% respectively, p < .01). There was no evidence that this difference was sex-specific (group by sex interaction p = .09), although overall, males had significantly lower shear strain than females (p = .02). Significant correlations were found in male subjects between thoracolumbar fascia shear strain and the following variables: perimuscular connective tissue thickness (r = -0.45, p <.001), echogenicity (r = -0.28, p < .05), trunk flexion range of motion (r = 0.36, p < .01), trunk extension range of motion (r = 0.41, p < .01), repeated forward bend task duration (r = -0.54, p < .0001) and repeated sit-to-stand task duration (r = -0.45, p < .001).ConclusionThoracolumbar fascia shear strain was ~20% lower in human subjects with chronic low back pain. This reduction of shear plane motion may be due to abnormal trunk movement patterns and/or intrinsic connective tissue pathology. There appears to be some sex-related differences in thoracolumbar fascia shear strain that may also play a role in altered connective tissue function.

Ultrasound evidence of altered lumbar connective tissue structure in human subjects with chronic low back pain.

BackgroundAlthough the connective tissues forming the fascial planes of the back have been hypothesized to play a role in the pathogenesis of chronic low back pain (LBP), there have been no previous studies quantitatively evaluating connective tissue structure in this condition. The goal of this study was to perform an ultrasound-based comparison of perimuscular connective tissue structure in the lumbar region in a group of human subjects with chronic or recurrent LBP for more than 12 months, compared with a group of subjects without LBP.MethodsIn each of 107 human subjects (60 with LBP and 47 without LBP), parasagittal ultrasound images were acquired bilaterally centered on a point 2 cm lateral to the midpoint of the L2-3 interspinous ligament. The outcome measures based on these images were subcutaneous and perimuscular connective tissue thickness and echogenicity measured by ultrasound.ResultsThere were no significant differences in age, sex, body mass index (BMI) or activity levels between LBP and No-LBP groups. Perimuscular thickness and echogenicity were not correlated with age but were positively correlated with BMI. The LBP group had ~25% greater perimuscular thickness and echogenicity compared with the No-LBP group (ANCOVA adjusted for BMI, p < 0.01 and p < 0.001 respectively).ConclusionThis is the first report of abnormal connective tissue structure in the lumbar region in a group of subjects with chronic or recurrent LBP. This finding was not attributable to differences in age, sex, BMI or activity level between groups. Possible causes include genetic factors, abnormal movement patterns and chronic inflammation.

Trunk muscular activation patterns and responses to transient force perturbation in persons with self-reported low back pain

Trunk stability requires muscle stiffness associated with appropriate timing and magnitude of activation of muscles. Abnormality of muscle function has been implicated as possible cause or consequence of back pain. This experimental study compared trunk muscle activation and responses to transient force perturbations in persons with and without self-reported history of low back pain. The objective was to determine whether or not history of back pain was associated with (1) altered anticipatory preactivation of trunk muscles or altered likelihood of muscular response to a transient force perturbation and (2) altered muscle activation patterns during a ramped effort. Twenty-one subjects who reported having back pain (LBP group) and twenty-three reporting no recent back pain (NLBP group) were tested while each subject stood in an apparatus with the pelvis immobilized. They performed ‘ramped-effort’ tests (to a voluntary maximum effort), and force perturbation tests. Resistance was provided by a horizontal cable from the thorax to one of five anchorage points on a wall track to the subject’s right at angles of 0°, 45°, 90°, 135° and 180° to the forward direction. In the perturbation tests, subjects first pulled against the cable to generate an effort nominally 15% or 30% of their maximum extension effort. The effort and the EMG activity of five right/left pairs of trunk muscles were recorded, and muscle responses were detected. In the ramped-effort tests the gradient of the EMG–effort relationship provided a measure of each muscle’s activation. On average, the LBP group subjects activated their dorsal muscles more than the NLBP group subjects in a maximum effort task when the EMG values were normalized for the maximum EMG, but this finding may have resulted from lesser maximum effort generated by LBP subjects. Greater muscle preactivation was recorded in the LBP group than the NLBP group just prior to the perturbation. The likelihood of muscle responses to perturbations was not significantly different between the two groups. The findings were consistent with the hypothesis that LBP subjects employed muscle activation in a quasi-static task and preactivation prior to a perturbation in an attempt to stiffen and stabilize the trunk. However, interpretation of the findings was complicated by the fact that LBP subjects generated lesser efforts, and it was not known whether this resulted from anatomical differences (e.g., muscle atrophy) or reduced motivation (e.g., pain avoidance).

FIBROBLAST CYTOSKELETAL REMODELING CONTRIBUTES TO CONNECTIVE TISSUE TENSION

The visco‐elastic behavior of connective tissue is generally attributed to the material properties of the extracellular matrix rather than cellular activity. We have previously shown that fibroblasts within areolar connective tissue exhibit dynamic cytoskeletal remodeling within minutes in response to tissue stretch ex vivo and in vivo. Here, we tested the hypothesis that fibroblasts, through this cytoskeletal remodeling, actively contribute to the visco‐elastic behavior of the whole tissue. We measured significantly increased tissue tension when cellular function was broadly inhibited by sodium azide and when cytoskeletal dynamics were compromised by disrupting microtubules (with colchicine) or actomyosin contractility (via Rho kinase inhibition). These treatments led to a decrease in cell body cross‐sectional area and cell field perimeter (obtained by joining the end of all of a fibroblasts processes). Suppressing lamellipodia formation by inhibiting Rac‐1 decreased cell body cross‐sectional area but did not affect cell field perimeter or tissue tension. Thus, by changing shape, fibroblasts can dynamically modulate the visco‐elastic behavior of areolar connective tissue through Rho‐dependent cytoskeletal mechanisms. These results have broad implications for our understanding of the dynamic interplay of forces between fibroblasts and their surrounding matrix, as well as for the neural, vascular, and immune cell populations residing within connective tissue. J. Cell. Physiol. 226: 1166–1175, 2011.

Comparison of three lumbar orthoses using motion assessment during task performance

Study Design. Four conditions (three orthoses, one no orthosis), full cross-over, randomized order, 12 subjects tested 3 months after a lumbar surgical arthrodesis. Objectives. To assess whole torso and lumbar motions and comfort for each orthoses condition during performance of activities of daily living. Summary of Background Data. Previous noninvasive studies measured whole torso (not just lumbar) movement. Recent development of a low profile, flexible, strain-gauged device (“Lordosimeter”) facilitated this study. Materials and Methods. The Lordosimeter was taped to the skin along the midline of the lumbosacral region. Orthoses studied were Boston anterior opening, Aspen lumbosacral, and Cybertech. Specified activities of daily living were performed for each orthosis condition. Subject effort during the flexion/extension task was assessed by surface electromyography (EMG). Comfort was assessed by visual analog scale. Results. There were no significant differences in EMG between orthoses. For lumbar flexion, trunk flexion, total lumbar motion, and total trunk motion, the mean values for Aspen and Boston (but not Cybertech) were significantly smaller than for no orthosis for most of the tasks and there were no significant differences between Aspen and Boston. The total lumbar motion allowed by each orthosis (averaged across tasks and relative to the no orthosis condition) was 81% for Aspen, 79% for Boston, and 97% for Cybertech. The comfort rating averaged across tasks was 2.24 for Aspen, 4.12 for Boston, and 3.92 for Cybertech (0 = very comfortable, 10 = very uncomfortable). Aspen was significantly more comfortable than Boston or Cybertech. Boston and Cybertech did not differ significantly. Conclusions. The Lordosimeter is useful for measuring lumbar motion during orthosis wear. The Aspen and the Boston orthoses provided significant flexion–extension motion restriction compared with no orthosis, but for almost all of the motion measures did not differ from each other. The Cybertech did not differ significantly from the no orthosis condition. The Aspen orthosis was rated significantly more comfortable than the Boston or the Cybertech.

Dynamic morphometric characterization of local connective tissue network structure in humans using ultrasound

BackgroundIn humans, connective tissue forms a complex, interconnected network throughout the body that may have mechanosensory, regulatory and signaling functions. Understanding these potentially important phenomena requires non-invasive measurements of collagen network structure that can be performed in live animals or humans. The goal of this study was to show that ultrasound can be used to quantify dynamic changes in local connective tissue structure in vivo. We first performed combined ultrasound and histology examinations of the same tissue in two subjects undergoing surgery: in one subject, we examined the relationship of ultrasound to histological images in three dimensions; in the other, we examined the effect of a localized tissue perturbation using a previously developed robotic acupuncture needling technique. In ten additional non-surgical subjects, we quantified changes in tissue spatial organization over time during needle rotation vs. no rotation using ultrasound and semi-variogram analyses.Results3-D renditions of ultrasound images showed longitudinal echogenic sheets that matched with collagenous sheets seen in histological preparations. Rank correlations between serial 2-D ultrasound and corresponding histology images resulted in high positive correlations for semi-variogram ranges computed parallel (r = 0.79, p < 0.001) and perpendicular (r = 0.63, p < 0.001) to the surface of the skin, indicating concordance in spatial structure between the two data sets. Needle rotation caused tissue displacement in the area surrounding the needle that was mapped spatially with ultrasound elastography and corresponded to collagen bundles winding around the needle on histological sections. In semi-variograms computed for each ultrasound frame, there was a greater change in the area under the semi-variogram curve across successive frames during needle rotation compared with no rotation. The direction of this change was heterogeneous across subjects. The frame-to-frame variability was 10-fold (p < 0.001) greater with rotation than with no rotation indicating changes in tissue structure during rotation.ConclusionThe combination of ultrasound and semi-variogram analyses allows quantitative assessment of dynamic changes in the structure of human connective tissue in vivo.

Ultrasound Evaluation of the Combined Effects of Thoracolumbar Fascia Injury and Movement Restriction in a Porcine Model

The persistence of back pain following acute back “sprains” is a serious public health problem with poorly understood pathophysiology. The recent finding that human subjects with chronic low back pain (LBP) have increased thickness and decreased mobility of the thoracolumbar fascia measured with ultrasound suggest that the fasciae of the back may be involved in LBP pathophysiology. This study used a porcine model to test the hypothesis that similar ultrasound findings can be produced experimentally in a porcine model by combining a local injury of fascia with movement restriction using a “hobble” device linking one foot to a chest harness for 8 weeks. Ultrasound measurements of thoracolumbar fascia thickness and shear plane mobility (shear strain) during passive hip flexion were made at the 8 week time point on the non-intervention side (injury and/or hobble). Injury alone caused both an increase in fascia thickness (p = .007) and a decrease in fascia shear strain on the non-injured side (p = .027). Movement restriction alone did not change fascia thickness but did decrease shear strain on the non-hobble side (p = .024). The combination of injury plus movement restriction had additive effects on reducing fascia mobility with a 52% reduction in shear strain compared with controls and a 28% reduction compared to movement restriction alone. These results suggest that a back injury involving fascia, even when healed, can affect the relative mobility of fascia layers away from the injured area, especially when movement is also restricted.

Differential displacement of soft tissue layers from manual therapy loading.

BACKGROUND Understanding the biomechanics of spinal manipulative therapy requires knowing how loads are transmitted to deeper structures. This investigation monitored displacement at sequential depths in thoracic paraspinal tissues parallel with surface load directions. METHODS Participants were prone and a typical preload maneuver was applied to thoracic tissues. Ultrasound speckle tracking synchronously monitored displacement and shear deformation of tissue layers in a region of interest adjacent to load application to a depth of 4 cm. Cumulative and shearing displacements along with myoelectric activity were quantitatively estimated adjacent to loading site. FINDINGS The cephalocaudal cumulative displacement in layers parallel to the surface were, in order of depth, 1.27 (SD=0.03), 1.18 (SD=0.02), and 1.06 (SD=0.01) mm (P<0.000), respectively. The superficial/intermediate shear was 2.1 ± 2.3% whereas the intermediate/deep shear was 4.4% (SE=3.7, P=0.014). Correlation of tissue layers was stronger with application site displacement at the surface (0.87<r<0.89) than with muscle activation (0.65<r<0.67). INTERPRETATION Surface loading of the torso in combined posteroanterior and caudocephalic directions result in both displacement of tissues anteriorly and in shearing between tissue layers in the plane of the tissues strata to depths that could plausibly affect spinal tissues. Displacements of tissues more likely arise passively, consistent with load transmitted by the retinacula cutis and epimuscular force pathways. Displacements are similar in magnitude to those known to evoke biologically relevant responses in both animal and human studies.

Effect of Stretching on Thoracolumbar Fascia Injury and Movement Restriction in a Porcine Model

Objective Stretching of fascia is an important component of manual and movement therapies. We previously showed that in pigs, a unilateral thoracolumbar fascia injury combined with movement restriction (hobble) produced contralateral loss of fascia mobility (shear strain during passive trunk flexion measured with ultrasound) similar to findings in human subjects with chronic low back pain. We now tested whether such abnormalities could be reversed by removing the hobble with or without daily stretching for 1 mo. Design Thirty pigs were randomized to control, injury, or injury + hobble for 8 wks. The hobble restricted hip extension ipsilateral to the injury. At week 8, the injury + hobble group was subdivided into continued hobble, removed hobble, and removed hobble + stretching (passively extending the hip for 10 min daily). Results Removing hobbles restored normal gait speed but did not restore fascia mobility. Daily passive stretching was not superior to removing hobbles, as there was no significant improvement in fascia mobility with either treatment group (removed hobble or stretching). Conclusions Reduced fascia mobility in response to injury and movement restriction worsens over time and persists even when movement is restored. Reversing fascia abnormalities may require either longer than 1 mo or a different treatment “dose” or modality.