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Biomedical subjects

Helene M Langevin

Publications and source records attributed to Helene M Langevin.

14 recordsLinked to original sources

Pathophysiological model for chronic low back pain integrating connective tissue and nervous system mechanisms.

Although chronic low back pain (cLBP) is increasingly recognized as a complex syndrome with multifactorial etiology, the pathogenic mechanisms leading to the development of chronic pain in this condition remain poorly understood. This article presents a new, testable pathophysiological model integrating connective tissue plasticity mechanisms with several well-developed areas of research on cLBP (pain psychology, postural control, neuroplasticity). We hypothesize that pain-related fear leads to a cycle of decreased movement, connective tissue remodeling, inflammation, nervous system sensitization and further decreased mobility. In addition to providing a new, testable framework for future mechanistic studies of cLBP, the integration of connective tissue and nervous system plasticity into the model will potentially illuminate the mechanisms of a variety of treatments that may reverse these abnormalities by applying mechanical forces to soft tissues (e.g. physical therapy, massage, chiropractic manipulation, acupuncture), by changing specific movement patterns (e.g. movement therapies, yoga) or more generally by increasing activity levels (e.g. recreational exercise). Non-invasive measures of connective tissue remodeling may eventually become important tools to evaluate and follow patients with cLBP in research and clinical practice. An integrative mechanistic model incorporating behavioral and structural aspects of cLBP will strengthen the rationale for a multidisciplinary treatment approach including direct mechanical tissue stimulation, movement reeducation, psychosocial intervention and pharmacological treatment to address this common and debilitating condition.

Adaptation, Physiological↗

Connective tissue: a body-wide signaling network?

Unspecialized "loose" connective tissue forms an anatomical network throughout the body. This paper presents the hypothesis that, in addition, connective tissue functions as a body-wide mechanosensitive signaling network. Three categories of signals are discussed: electrical, cellular and tissue remodeling, each potentially responsive to mechanical forces over different time scales. It is proposed that these types of signals generate dynamic, evolving patterns that interact with one another. Such connective tissue signaling would be affected by changes in movement and posture, and may be altered in pathological conditions (e.g. local decreased mobility due to injury or pain). Connective tissue thus may function as a previously unrecognized whole body communication system. Since connective tissue is intimately associated with all other tissues (e.g. lung, intestine), connective tissue signaling may coherently influence (and be influenced by) the normal or pathological function of a wide variety of organ systems. Demonstrating the existence of a connective signaling network therefore may profoundly influence our understanding of health and disease.

Animals↗

Fibroblast spreading induced by connective tissue stretch involves intracellular redistribution of alpha- and beta-actin.

Mechanical stretching of connective tissue occurs with normal movement and postural changes, as well as treatments including physical therapy, massage and acupuncture. Connective tissue fibroblasts were recently shown to respond actively to short-term mechanical stretch (minutes to hours) with reversible cytoskeletal remodeling, characterized by extensive cell spreading and lamellipodia formation. In this study, we have examined the effect of tissue stretch on the distribution of alpha- and beta-actin in subcutaneous tissue fibroblasts ex vivo. Normal fibroblasts uniformly exhibited alpha-smooth muscle actin (alpha-SMA) immunoreactivity. Unlike cultured fibroblasts and smooth muscle cells, alpha-SMA in these fibroblasts was not in F-actin form (indicated by lack of phalloidin co-localization) nor was it organized into distinct stress fibers. The lack of stress fibers and fibronexus was confirmed by electron microscopy, indicating that these cells were not myofibroblasts. In unstretched tissue, the pattern of alpha-actin was diffuse and granular. With tissue stretch (30 min), alpha-actin formed a star-shaped pattern centered on the nucleus, while beta-actin extended throughout the cytoplasm including lamellipodia and cell cortex. This dual response pattern of alpha- and beta-actin may be an important component of cellular mechanotransduction mechanisms relevant to physiologic and therapeutic mechanical forces applied to connective tissue.

Actins↗

Subcutaneous tissue fibroblast cytoskeletal remodeling induced by acupuncture: evidence for a mechanotransduction-based mechanism.

Acupuncture needle rotation has been previously shown to cause specific mechanical stimulation of subcutaneous connective tissue. This study uses acupuncture to investigate the role of mechanotransduction-based mechanisms in mechanically-induced cytoskeletal remodeling. The effect of acupuncture needle rotation was quantified by morphometric analysis of mouse tissue explants imaged with confocal microscopy. Needle rotation induced extensive fibroblast spreading and lamellipodia formation within 30 min, measurable as an increased in cell body cross sectional area. The effect of rotation peaked with two needle revolutions and decreased with further increases in rotation. Significant effects of rotation were present throughout the tissue, indicating the presence of a response extending laterally over several centimeters. The effect of rotation with two needle revolutions was prevented by pharmacological inhibitors of actomyosin contractility (blebbistatin), Rho kinase (Y-27632 and H-1152), and Rac signaling. The active cytoskeletal response of fibroblasts demonstrated in this study constitutes an important step in understanding cellular mechanotransduction responses to externally applied mechanical stimuli in whole tissue, and supports a previously proposed model for the mechanism of acupuncture involving connective tissue mechanotransduction.

Acupuncture↗

Electrical impedance along connective tissue planes associated with acupuncture meridians.

BACKGROUND: Acupuncture points and meridians are commonly believed to possess unique electrical properties. The experimental support for this claim is limited given the technical and methodological shortcomings of prior studies. Recent studies indicate a correspondence between acupuncture meridians and connective tissue planes. We hypothesized that segments of acupuncture meridians that are associated with loose connective tissue planes (between muscles or between muscle and bone) visible by ultrasound have greater electrical conductance (less electrical impedance) than non-meridian, parallel control segments. METHODS: We used a four-electrode method to measure the electrical impedance along segments of the Pericardium and Spleen meridians and corresponding parallel control segments in 23 human subjects. Meridian segments were determined by palpation and proportional measurements. Connective tissue planes underlying those segments were imaged with an ultrasound scanner. Along each meridian segment, four gold-plated needles were inserted along a straight line and used as electrodes. A parallel series of four control needles were placed 0.8 cm medial to the meridian needles. For each set of four needles, a 3.3 kHz alternating (AC) constant amplitude current was introduced at three different amplitudes (20, 40, and 80 microAmps) to the outer two needles, while the voltage was measured between the inner two needles. Tissue impedance between the two inner needles was calculated based on Ohm's law (ratio of voltage to current intensity). RESULTS: At the Pericardium location, mean tissue impedance was significantly lower at meridian segments (70.4 +/- 5.7 Omega) compared with control segments (75.0 +/- 5.9 Omega) (p = 0.0003). At the Spleen location, mean impedance for meridian (67.8 +/- 6.8 Omega) and control segments (68.5 +/- 7.5 Omega) were not significantly different (p = 0.70). CONCLUSION: Tissue impedance was on average lower along the Pericardium meridian, but not along the Spleen meridian, compared with their respective controls. Ultrasound imaging of meridian and control segments suggested that contact of the needle with connective tissue may explain the decrease in electrical impedance noted at the Pericardium meridian. Further studies are needed to determine whether tissue impedance is lower in (1) connective tissue in general compared with muscle and (2) meridian-associated vs. non meridian-associated connective tissue.

Adult↗

Dynamic fibroblast cytoskeletal response to subcutaneous tissue stretch ex vivo and in vivo.

Cytoskeleton-dependent changes in cell shape are well-established factors regulating a wide range of cellular functions including signal transduction, gene expression, and matrix adhesion. Although the importance of mechanical forces on cell shape and function is well established in cultured cells, very little is known about these effects in whole tissues or in vivo. In this study we used ex vivo and in vivo models to investigate the effect of tissue stretch on mouse subcutaneous tissue fibroblast morphology. Tissue stretch ex vivo (average 25% tissue elongation from 10 min to 2 h) caused a significant time-dependent increase in fibroblast cell body perimeter and cross-sectional area (ANOVA, P < 0.01). At 2 h, mean fibroblast cell body cross-sectional area was 201% greater in stretched than in unstretched tissue. Fibroblasts in stretched tissue had larger, "sheetlike" cell bodies with shorter processes. In contrast, fibroblasts in unstretched tissue had a "dendritic" morphology with smaller, more globular cell bodies and longer processes. Tissue stretch in vivo for 30 min had effects that paralleled those ex vivo. Stretch-induced cell body expansion ex vivo was inhibited by colchicine and cytochalasin D. The dynamic, cytoskeleton-dependent responses of fibroblasts to changes in tissue length demonstrated in this study have important implications for our understanding of normal movement and posture, as well as therapies using mechanical stimulation of connective tissue including physical therapy, massage, and acupuncture.

Actins↗

Fibroblasts form a body-wide cellular network.

"Loose" connective tissue forms a network extending throughout the body including subcutaneous and interstitial connective tissues. The existence of a cellular network of fibroblasts within loose connective tissue may have considerable significance as it may support yet unknown body-wide cellular signaling systems. We used a combination of histochemistry, immunohistochemistry, confocal scanning laser microscopy (confocal microscopy), and electron microscopy to investigate the extent and nature of cell-to-cell connections within mouse subcutaneous connective tissue. We found that fibroblasts formed a reticular web throughout the tissue. With confocal microscopy, 30% of fibroblasts' processes could be followed continuously from one cell to another. Connexin 43 immunoreactivity was present at apparent points of cell-to-cell contact. Electron microscopy revealed that processes from adjacent cells were in close apposition to one another, but gap junctions were not observed. Our findings indicate that soft tissue fibroblasts form an extensively interconnected cellular network, suggesting they may have important and so far unsuspected integrative functions at the level of the whole body.

Animals↗

Tissue displacements during acupuncture using ultrasound elastography techniques.

Acupuncture needle manipulation has been previously shown to result in measurable changes in connective tissue architecture in animal experiments. In this study, we used a novel in vivo ultrasound (US)-based technique to quantify tissue displacement during acupuncture manipulation in humans. B-scan ultrasonic imaging was performed on the thighs of 12 human subjects at different stages of needle motion, including varying amounts of rotation, downward and upward movement performed with a computer-controlled acupuncture needling instrument. Tissue displacements, estimated using cross-correlation techniques, provided successful mapping and quantitative analysis of spatial and temporal tissue behavior during acupuncture needle manipulation. Increasing amounts of rotation had a significant linear effect on tissue displacement during downward and upward needle motion, as well as on rebound tissue displacement after downward needle movement. In addition to being a valuable tool for studies of acupuncture's mechanism of action, this technique may have applications to other types of needling including biopsies.

Acupuncture Therapy↗

Yin scores and yang scores: A new method for quantitative diagnostic evaluation in traditional Chinese medicine research.

OBJECTIVE: To develop and evaluate a method for quantitative evaluation of yin and yang (yin and yang scores) in human subjects for the purposes of research. This method aims to classify subjects into groups allowing future quantitative testing of key research questions such as: do different groups of patients respond differently to acupuncture treatments or Chinese herb formulas? METHODS: In a pilot study of inter-rater reliability, 12 volunteers were each successively interviewed and examined by 6 acupuncturists on the same day. Each acupuncturist gave each volunteer a score for yin and a score for yang on a scale of -10 to +10, zero representing a "balanced" score. Acupuncturists were blinded to each other's scores. RESULTS: Overall mean (+/-standard deviation [SD]) yin and yang scores were -1.86 +/- 0.90 and -0.68 +/- 1.23 respectively. Intraclass correlations (ICCs) associated with a single acupuncturist's ratings were 0.35 (yin) and 0.36 (yang). ICC's for subject's mean scores based on the six acupuncturists were 0.77 (yin) and 0.78 (yang). Significant differences in mean scores across subjects were detected for yin (p < 0.001) and yang (p < 0.001) (repeated-measures analysis of variance [ANOVA]) based on the multiple acupuncturists' ratings. CONCLUSION: These results indicate that (1) yin and yang can be quantified in a reliable manner, but evaluation by multiple acupuncturists is necessary to obtain a reliable score; (2) yin and yang scores can be used to group individuals for the purposes of statistical analysis. Further evaluation of yin and yang scores in a greater number and wider variety of patients will be needed to evaluate the potential usefulness of this measurement tool in acupuncture clinical trials and basic physiologic research.

Acupuncture↗

Subcutaneous tissue mechanical behavior is linear and viscoelastic under uniaxial tension.

Subcutaneous tissue is part of a bodywide network of "loose" connective tissue including interstitial connective tissues separating muscles and surrounding all nerves and blood vessels. Despite its ubiquitous presence in the body and its potential importance in a variety of therapies utilizing mechanical stretch, as well as normal movement and exercise, very little is known about loose connective tissue's biomechanical behavior. This study aimed to determine elastic and viscoelastic mechanical properties of ex-vivo rat subcutaneous tissue in uniaxial tension with incremental stress relaxation experiments. The elastic response of the tissue was linear, with instantaneous and equilibrium tensile moduli of 4.77 kPa and 2.75 kPa, respectively. Using a 5 parameter Maxwell solid model, material parameters micro(1) = 0.95 +/- 0.24 Ns/m and micro(2) = 8.49 +/- 2.42 Ns/m defined coefficients of viscosity related to time constants tau(1M) = 3.83 +/- 0.15 sec and tau(2M) = 30.15 +/- 3.16 sec, respectively. Using a continuous relaxation function, parameters C = 0.25 +/- 0.12, tau(1C) = 1.86 +/- 0.34 sec, and tau(2C) = 110.40 +/- 25.59 sec defined the magnitude and frequency limits of the relaxation spectrum. This study provides baseline information for the stress-strain behaviors of subcutaneous connective tissue. Our results underscore the differences in mechanical behaviors between loose and high-load bearing connective tissues and suggest that loose connective tissues may function to transmit mechanical signals to and from the abundant fibroblasts, immune, vascular, and neural cells present within these tissues.

Animals↗

Relationship of acupuncture points and meridians to connective tissue planes.

Acupuncture meridians traditionally are believed to constitute channels connecting the surface of the body to internal organs. We hypothesize that the network of acupuncture points and meridians can be viewed as a representation of the network formed by interstitial connective tissue. This hypothesis is supported by ultrasound images showing connective tissue cleavage planes at acupuncture points in normal human subjects. To test this hypothesis, we mapped acupuncture points in serial gross anatomical sections through the human arm. We found an 80% correspondence between the sites of acupuncture points and the location of intermuscular or intramuscular connective tissue planes in postmortem tissue sections. We propose that the anatomical relationship of acupuncture points and meridians to connective tissue planes is relevant to acupuncture's mechanism of action and suggests a potentially important integrative role for interstitial connective tissue.

Acupuncture↗

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 acupuncture's therapeutic mechanism.

Acupuncture↗