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While our understanding of pain is rapidly growing, some areas of pain research are lagging behind. This article discusses two current and inter-related gaps in knowledge that are in need of addressing: first, the connections between “brain” and “body” components of pain; and second, the process of endogenous pain resolution. Historical reasons for these research gaps are discussed and solutions are outlined based on an integrative, whole person research approach. These include comprehensive mapping of the mechanosensory and nociceptive innervation of deep tissues; developing objective, non-invasive measurements to quantify the metabolic, structural and mechanical components of the peripheral tissue environment; integrating our understanding of pain pathophysiology, across whole organs and whole body, as well as across bio-psycho-social domains; and understanding the interplay of nervous system and peripheral tissue mechanisms that promote the endogenous resolution of pain and prevent its acute-to-chronic transition. Current NIH-led efforts in these areas are outlined, including several studies within the NIH HEAL (or Help End Addition Long Term) initiative and the National Center for Complementary and Integrative Health’s strategic priorities in whole person research. [ABSTRACT FROM AUTHOR]

Background: Our conventional approach to health care tends to separate patients' health by body system, treating each independently and "efficiently"—e.g., minimal time with a provider, reliance on medications, and little investment to support behavioral and lifestyle improvements. Meanwhile, the United States has the most expensive health care in the world, with some of the worse outcomes. Purpose In this paper, we make the case for transforming health care from a disease-centric approach to a "whole person" model. Research Design: We provide detailed health and health care utilization assumptions for a hypothetical patient, Mrs. M, over her life from age 40 to 80 years under 2 care scenarios: the continuation of conventional care (Version A) and a whole person care approach (Version B). Analysis We developed a set of health care utilization assumptions for each scenario, applied 2023 U.S. dollar (USD) resource prices, and estimated cumulative total health care costs. The price and the health care utilization assumptions for the conventional care scenario were validated using Medical Expenditures Panel Survey (MEPS) data. Results: At age 80, with conventional care, we find Mrs. M increasingly frail and living in a skilled nursing facility, with total cumulative health care costs of $353,155. With whole person care, we find her active and generally healthy at age 80, with total cumulative health care costs of $52,425. Conclusions: Although based on an "imagined" case, the 2 versions of Mrs. M's history illustrate how an investment beginning in early middle age to support a healthy diet, physical activity, and stress management can plausibly lead to improved health and well-being, as well as reduced health care spending. [ABSTRACT FROM AUTHOR]

Healthy aging is an integrated "whole person" process that involves an individual's biology, behavior, and social/physical environment. With the recent development of antiaging drugs, careful consideration of the respective roles of pharmacologic and nonpharmacologic approaches to both health and aging is in order. Recent advances in understanding the cellular and molecular mechanisms of aging are providing new measures that can be used as clinical outcomes in studying the impact of antiaging interventions in humans. This paper outlines the strategic interest of the National Center for Complementary and Integrative Health (NCCIH) in supporting the development, testing, and implementation of effective, scalable, and integrated multicomponent interventions to support healthy aging of the whole person. [ABSTRACT FROM AUTHOR]

Understanding the factors that influence the biological response to inflammation is crucial, due to its involvement in physiological and pathological processes, including tissue repair/healing, cancer, infections, and autoimmune diseases. We have previously demonstrated that in vivo stretching can reduce inflammation and increase local pro‐resolving lipid mediators in rats, suggesting a direct mechanical effect on inflammation resolution. Here we aimed to explore further the effects of stretching at the cellular/molecular level in a mouse subcutaneous carrageenan‐inflammation model. Stretching for 10 min twice a day reduced inflammation, increased the production of pro‐resolving mediator pathway intermediate 17‐HDHA at 48 h postcarrageenan injection, and decreased both pro‐resolving and pro‐inflammatory mediators (e.g., PGE2 and PGD2) at 96 h. Single‐cell RNA sequencing analysis of inflammatory lesions at 96 h showed that stretching increased the expression of both pro‐inflammatory (Nos2) and pro‐resolution (Arg1) genes in M1 and M2 macrophages at 96 h. An intercellular communication analysis predicted specific ligand–receptor interactions orchestrated by neutrophils and M2a macrophages, suggesting a continuous neutrophil presence recruiting immune cells such as activated macrophages to contain the antigen while promoting resolution and preserving tissue homeostasis. [ABSTRACT FROM AUTHOR]

The article provides information on the concept of resilience in the health sciences, which encompasses the ability to respond to various challenges, both physiological and psychological. It discusses how the National Institutes of Health (NIH) defines resilience as the capacity to resist, recover, adapt, or grow from challenges and illustrates examples of resilience in the context of physiological responses.

Complementary and integrative health approaches can improve health and well‐being, as well as play an important role in disease prevention. The concept of whole person health builds on these concepts by empowering individuals, families, communities, and populations to improve their health in multiple interconnected domains: biological, behavioural, social, and environmental. Research on whole person health involves studies of interconnected biological systems and complex approaches to prevention and treatment. Some of these approaches may involve methods of diagnosis and therapy that differ from those used in conventional Western medicine. Of growing interest is how complementary, integrative, and whole person health approaches contribute to resilience. This brief commentary describes an integrated framework for mapping the connections between various complementary and integrative health therapeutic inputs onto aspects of resilience, including the ability to resist, recover (partially or fully), adapt, and/or grow in response to a following a stressor. The authors present selected examples of research studies supported by the National Institutes of Health that test whether complementary and integrative health approaches can promote some aspect of resilience. We conclude with a discussion of the challenges and opportunities in incorporating the study of resilience in complementary, integrative, and whole person health research. [ABSTRACT FROM AUTHOR]

In an ongoing series of spotlight interviews, Challenges Advisory Board Member and Nova Institute for Health Fellow, Alan C. Logan, meets with thought leaders, scientists, scholars, healthcare professionals, artisans and visionaries concerned about health at scales of persons, places and the planet. Here in the inaugural interview, the Director of the National Institutes of Health, National Center for Complementary and Integrative Health, Dr. Helene Langevin, responds to a set of questions posed by Challenges. Dr. Langevin discusses the emerging concept of whole person health, and in particular, how the concept intersects with the grand and interconnected challenges of our time. [ABSTRACT FROM AUTHOR]

This issue of Global Advances in Health and Medicine sends a vital message about the importance of whole person health. Whole person health rests on the idea that our health involves multiple interconnected factors across physiological systems, as well as biological, behavioral, social, and environmental domains. The urgency of better understanding whole person health is highlighted by the current global health crisis. Yet, biomedical research often favors a reductionist approach. The current emphasis on diseases or single organ systems can fall short when it comes to addressing the interconnected factors that contribute to worse health outcomes. This, coupled with a fragmented health care delivery system, contributes to the challenges that patients face every day in becoming healthier. As part of the U.S. National Institutes of Health, our role at the National Center for Complementary and Integrative Health (NCCIH) is to foster research in this field. NCCIH's twenty years of research has built a body of knowledge that has established a clear path forward for exploring whole person health in the coming years. Within the framework of our strategic plan, NCCIH is working to build research methods for studying whole person health and explore how this understanding of health can transform the way complementary and integrative health is perceived and implemented within the wider health care delivery system.The collection of papers highlighted in this month's issue of Global Advances in Health and Medicine sends an important and encouraging signal about the efforts being made to deliver health care in a way that recognizes the importance of whole person health. Each of these studies provides new insights on how stakeholders might approach transforming the delivery of health care, integrating approaches that can improve health outcomes for people. [ABSTRACT FROM AUTHOR]

Abstract Background The 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). Methods We 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. Results Thoracolumbar 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 Conclusion Thoracolumbar 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.

Abstract Background Although 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. Methods In 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. Results There 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). Conclusion This 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.

The article focuses on moving the Complementary and Integrative Health Research Field Toward Whole Person Health. Topics discussed include the mindset for whole person health is borne out of pragmatic challenges see every day in the experiences of patients and the stubbornly persistent and interconnected factors that can lead people into a poor state of health; and the current health crises have galvanized us to better understand the importance of the environment as a determinant of health.

Abstract 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 μAmps) 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 Ω) compared with control segments (75.0 ± 5.9 Ω) (p = 0.0003). At the Spleen location, mean impedance for meridian (67.8 ± 6.8 Ω) and control segments (68.5 ± 7.5 Ω) 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.

Objective: Although less is known about musculoskeletal factors that may contribute to asthma symptoms, body-based treatments addressing movement restrictions of the chest and shoulders may be a useful adjunct to asthma pharmacotherapy. In this pilot study, we compared asthma symptoms, pulmonary function tests, and medication use before and after a course of resistance flexibility and strength training (RFST) treatments in human subjects with asthma. Methods: Patients with asthma (n = 10; mean age 23 years) completed questionnaires (Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Test (ACT)), spirometry, chest wall excursion, and shoulder range of motion (ROM) before and after a series of four RFST treatments over 47 ± 21 days. Each treatment consisted of a one-hour session involving eccentric stretching of the arm, shoulder, and chest while lying in a supine position. Results: Significant clinical improvement was observed for mean ACQ scores from pre- to post-treatment (mean decrease 0.73, 95% CI 0.26-1.09, Cohen d = 2.25, p =.0014). No significant improvement was observed in the ACT, AQLQ, or spirometry, although inhaler use decreased for half of the subjects and did not change for the remaining subjects (i.e. none increased). Chest wall excursion and all ROM tests trended toward improvement, but was only statistically significant (p <.05) for the arm raise in the frontal plane. Conclusion: RFST may be a beneficial, nonpharmacological method to decrease asthma symptoms. Future studies should be conducted involving a larger sample size, longer intervention time, control group, and blood collection to test inflammatory mediators. [ABSTRACT FROM AUTHOR]

Despite having made substantial progress in academic rigor over the past decades, acupuncture research has been the focus of long-standing and persistent attacks by skeptics. One recurring theme of critics is that the concept of acupuncture points has no scientific validity. Meanwhile, the subject of whether-or-not acupuncture points ''exist'' has been given too little attention within the acupuncture research community. In this article, we argue that failure to use clear terminology and rigorously investigate the subject of acupuncture points has hindered the growing legitimacy of acupuncture as an evidence-based therapy. We propose that a coordinated effort is needed to improve the use of terminology related to acupuncture points, combined with rigorous investigation of their ''specificity'' and possible biological basis. [ABSTRACT FROM AUTHOR]

The article proposes that some components of acupuncture missing from the Traditional Chinese Medicine (TCM) model are related to important advances in physiology and medicine. Topics discussed include differences in the diagnostic process in Western medicine, TCM, and classical Chinese medicine, musculoskeletal system as one system that remained separate and outside of internal medicine, and a basic component of classic Chinese medicine that emerged early on.

Objective: Although physical therapy can help preserve mobility in patients with systemic sclerosis (SSc), stretching has not been used systematically as a treatment to prevent or reverse the disease process. We previously showed in rodent models that stretching promotes the resolution of connective tissue inflammation and reduces new collagen formation after injury. Here, we tested the hypothesis that stretching would impact scleroderma development using a mouse sclerodermatous graft-versus-host disease (sclGvHD) model. Methods: The model consists in the adoptive transfer (allogeneic) of splenocytes from B10.D2 mice (graft) into Rag2-/- BALB/c hosts (sclGvHD), resulting in skin inflammation followed by fibrosis over 4 weeks. SclGvHD mice and controls were randomized to stretching in vivo for 10 min daily versus no stretching. Results: Weekly ultrasound measurements of skin thickness and subcutaneous tissue mobility in the back (relative tissue displacement during passive trunk motion) successfully captured the different phases of the sclGvHD model. Stretching reduced skin thickness and increased subcutaneous tissue mobility compared to no stretching at week 3. Stretching also reduced the expression of CCL2 and ADAM8 in the skin at week 4, which are two genes known to be upregulated in both murine sclGvHD and the inflammatory subset of human SSc. However, there was no evidence that stretching attenuated inflammation at week 2. Conclusion: Daily stretching for 10 min can improve skin thickness and mobility in the absence of any other treatment in the sclGvHD murine model. These pre-clinical results suggest that a systematic investigation of stretching as a therapeutic modality is warranted in patients with SSc. [ABSTRACT FROM AUTHOR]

Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators (SPMs), including resolvins, that orchestrate the resolution of local inflammation. We showed earlier that, in rats with subcutaneous inflammation of the back induced by carrageenan, stretching for 10 min twice daily reduced inflammation and improved pain, 2 weeks after carrageenan injection. In this study, we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation. In rats injected with carrageenan and randomized to stretch versus no stretch for 48 h, stretching reduced inflammatory lesion thickness and neutrophil count, and increased resolvin (RvD1) concentrations within lesions. Furthermore, subcutaneous resolvin injection mimicked the effect of stretching. In ex vivo experiments, stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration. These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue. J. Cell. Physiol. 231: 1621-1627, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Research into acupuncture has had ripple effects beyond the field of acupuncture. This paper identifies five exemplars to illustrate that there is tangible evidence of the way insights gleaned from acupuncture research have informed biomedical research, practice, or policy. The first exemplar documents how early research into acupuncture analgesia has expanded into neuroimaging research, broadening physiologic understanding and treatment of chronic pain. The second describes how the acupuncture needle has become a tool to enhance biomedical knowledge of connective tissue. The third exemplar, which illustrates use of a modified acupuncture needle as a sham device, focuses on emergent understanding of placebo effects and, in turn, on insights into therapeutic encounters in treatments unrelated to acupuncture. The fourth exemplar documents that two medical devices now in widespread use were inspired by acupuncture: transcutaneous electrical nerve stimulators for pain control and antinausea wrist bands. The final exemplar describes how pragmatic clinical trial designs applied in acupuncture research have informed current general interest in comparative effectiveness research. In conclusion, these exemplars of unanticipated outcomes of acupuncture research comprise an additional rationale for continued support of basic and clinical research evaluating acupuncture and other under-researched therapies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In the field of acupuncture research there is an implicit yet unexplored assumption that the evidence on manual and electrical stimulation techniques, derived from basic science studies, clinical trials, systematic reviews, and meta-analyses, is generally interchangeable. Such interchangeability would justify a bidirectional approach to acupuncture research, where basic science studies and clinical trials each inform the other. This article examines the validity of this fundamental assumption by critically reviewing the literature and comparing manual to electrical acupuncture in basic science studies, clinical trials, and meta-analyses. The evidence from this study does not support the assumption that these techniques are interchangeable. This article also identifies endemic methodologic limitations that have impaired progress in the field. For example, basic science studies have not matched the frequency and duration of manual needle stimulation to the frequency and duration of electrical stimulation. Further, most clinical trials purporting to compare the two types of stimulation have instead tested electroacupuncture as an adjunct to manual acupuncture. The current findings reveal fundamental gaps in the understanding of the mechanisms and relative effectiveness of manual versus electrical acupuncture. Finally, future research directions are suggested to better differentiate electrical from manual simulation, and implications for clinical practice are discussed. [ABSTRACT FROM AUTHOR]

Total Force Fitness (TFF) was conceived as a holistic framework for building and sustaining Human Performance Optimization for Warfighters and their families. As such, TFF research must also be holistic in nature. During the research breakout, group barriers and challenges to TFF research were discussed, and critical research focus areas were prioritized. The top approaches discussed were (1) using big data to identify best practices and health trajectories; (2) applying community-based participatory research principles to military units; (3) focusing on "Whole-Person," integrative research (physical, behavioral, spiritual, and biological) across the Department of Defense; and, finally, (4) prioritizing key opportunities to advance TFF across the active duty and Reserve/Guard enterprises and their families. The research group noted that coordinated action would be needed to move the prioritized agenda forward. Finally, translating research into action is essential because TFF is a way of honoring our service members as whole persons with careers, goals, and families. [ABSTRACT FROM AUTHOR]

Objectives: Acupuncture needle manipulation causes mechanical deformation of connective tissue, which in turn results in mechanical stimulation of fibroblasts, with active changes in cell shape and autocrine purinergic signaling. We have previously shown using ultrasound elastography in humans that acupuncture needle manipulation causes measurable movement of tissue up to several centimeters away from the needle. The goal of this study was to quantify the spatial pattern of tissue displacement and deformation (shear strain) in response to acupuncture needling along an intermuscular connective tissue plane compared with needling over the belly of a muscle. Design: Eleven (11) healthy human subjects underwent a single testing session during which robotic acupuncture needling was performed while recording tissue displacement using ultrasound. Outcome measures were axial and lateral tissue displacement as well as lateral shear strain calculated using ultrasound elastography postprocessing. Results: Tissue displacement and strain extended further in the longitudinal direction when needling between muscles, and in the transverse direction when needling over the belly of a muscle. Conclusions: The anisotropic tissue motion observed in this study may influence the spatial distribution of local connective tissue cellular responses following acupuncture needle manipulation. [ABSTRACT FROM AUTHOR]

Objective: Although physical therapy can help preserve mobility in patients with systemic sclerosis (SSc), stretching has not been used systematically as a treatment to prevent or reverse the disease process. We previously showed in rodent models that stretching promotes the resolution of connective tissue inflammation and reduces new collagen formation after injury. Here, we tested the hypothesis that stretching would impact scleroderma development using a mouse sclerodermatous graft-versus-host disease (sclGvHD) model. Methods: The model consists in the adoptive transfer (allogeneic) of splenocytes from B10.D2 mice (graft) into Rag2−/− BALB/c hosts (sclGvHD), resulting in skin inflammation followed by fibrosis over 4 weeks. SclGvHD mice and controls were randomized to stretching in vivo for 10 min daily versus no stretching. Results: Weekly ultrasound measurements of skin thickness and subcutaneous tissue mobility in the back (relative tissue displacement during passive trunk motion) successfully captured the different phases of the sclGvHD model. Stretching reduced skin thickness and increased subcutaneous tissue mobility compared to no stretching at week 3. Stretching also reduced the expression of CCL2 and ADAM8 in the skin at week 4, which are two genes known to be upregulated in both murine sclGvHD and the inflammatory subset of human SSc. However, there was no evidence that stretching attenuated inflammation at week 2. Conclusion: Daily stretching for 10 min can improve skin thickness and mobility in the absence of any other treatment in the sclGvHD murine model. These pre-clinical results suggest that a systematic investigation of stretching as a therapeutic modality is warranted in patients with SSc.

Fibroblasts in whole areolar connective tissue respond to static stretching of the tissue by expanding and remodeling their cytoskeleton within minutes both ex vivo and in vivo. This study tested the hypothesis that the mechanism of fibroblast expansion in response to tissue stretch involves extracellular ATP signaling. In response to tissue stretch ex vivo, ATP levels in the bath solution increased significantly, and this increase was sustained for 20 min, returning to baseline at 60 min. No increase in ATP was observed in tissue incubated without stretch or tissue stretched in the presence of the Rho kinase inhibitor Y27632. The increase in fibroblast cross sectional area in response to tissue stretch was blocked by both suramin (a purinergic receptor blocker) and apyrase (an enzyme that selectively degrades extracellular ATP). Furthermore, connexin channel blockers (octanol and carbenoxolone), but not VRAC (fluoxetine) or pannexin (probenecid) channel blockers, inhibited fibroblast expansion. Together, these results support a mechanism in which extracellular ATP signaling via connexin hemichannels mediate the active change in fibroblast shape that occurs in response to a static increase in tissue length. J. Cell. Physiol. 228: 1922-1926, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In areolar 'loose' connective tissue, fibroblasts remodel their cytoskeleton within minutes in response to static stretch resulting in increased cell body cross-sectional area that relaxes the tissue to a lower state of resting tension. It remains unknown whether the loosely arranged collagen matrix, characteristic of areolar connective tissue, is required for this cytoskeletal response to occur. The purpose of this study was to evaluate cytoskeletal remodeling of fibroblasts in, and dissociated from, areolar and dense connective tissue in response to 2 h of static stretch in both native tissue and collagen gels of varying crosslinking. Rheometric testing indicated that the areolar connective tissue had a lower dynamic modulus and was more viscous than the dense connective tissue. In response to stretch, cells within the more compliant areolar connective tissue adopted a large 'sheet-like' morphology that was in contrast to the smaller dendritic morphology in the dense connective tissue. By adjusting the in vitro collagen crosslinking, and the resulting dynamic modulus, it was demonstrated that cells dissociated from dense connective tissue are capable of responding when seeded into a compliant matrix, while cells dissociated from areolar connective tissue can lose their ability to respond when their matrix becomes stiffer. This set of experiments indicated stretch-induced fibroblast expansion was dependent on the distinct matrix material properties of areolar connective tissues as opposed to the cells' tissue of origin. These results also suggest that disease and pathological processes with increased crosslinks, such as diabetes and fibrosis, could impair fibroblast responsiveness in connective tissues. J. Cell. Physiol. 228: 50-57, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives: The highly variable nature of acupuncture needling creates challenges to systematic research. The goal of this study was to test the feasibility of quantifying acupuncture needle manipulation using motion and force measurements. It was hypothesised that distinct needling styles and techniques would produce different needle motion and force patterns that could be quantified and differentiated from each other. Methods: A new needling sensor tool (Acusensor) was used to record needling in real time as performed by six New England School of Acupuncture staff from the 'Chinese acupuncture' (style 1) and 'Japanese acupuncture' (style 2) programmes (three from each). Each faculty expert needled 12 points (6 bilateral locations) in 12 healthy human subjects using tonification (technique 1) and dispersal (technique 2). Parameters calculated from the raw needling data were displacement amplitude, displacement frequency, rotation amplitude, rotation frequency, force amplitude and torque amplitude. Results: Data analysis revealed significant differences in the amplitude of displacement and rotation between needling performed by staff from two different acupuncture styles. Significant overall differences in the frequency of displacement between techniques 1 and 2 that were not dependent of the style of acupuncture being performed were also found. The relationships between displacement and rotation frequencies, as well as between displacement and force amplitudes showed considerable variability across individual acupuncturists and subjects. Conclusions: Needling motion and force parameters can be quantified in a treatment-like setting. Needling data can subsequently be analysed, providing an objective method for characterising needling in basic and clinical acupuncture research. [ABSTRACT FROM AUTHOR]

The role played by nonspecialized connective tissues in chronic non-specific low back pain is not well understood. In a recent ultrasound study, human subjects with chronic low back pain had altered connective tissue structure compared to human subjects without low back pain, suggesting the presence of inflammation and/or fibrosis in the low back pain subjects. Mechanical input in the form of static tissue stretch has been shown in vitro and in vivo to have anti-inflammatory and anti-fibrotic effects. To better understand the pathophysiology of lumbar nonspecialized connective tissue as well as potential mechanisms underlying therapeutic effects of tissue stretch, we developed a carrageenan-induced inflammation model in the low back of a rodent. Induction of inflammation in the lumbar connective tissues resulted in altered gait, increased mechanical sensitivity of the tissues of the low back, and local macrophage infiltration. Mechanical input was then applied to this model as in vivo tissue stretch for 10 minutes twice a day for 12 days. In vivo tissue stretch mitigated the inflammation-induced changes leading to restored stride length and intrastep distance, decreased mechanical sensitivity of the back and reduced macrophage expression in the nonspecialized connective tissues of the low back. This study highlights the need for further investigation into the contribution of connective tissue to low back pain and the need for a better understanding of how interventions involving mechanical stretch could provide maximal therapeutic benefit. This tissue stretch research is relevant to body-based treatments such as yoga or massage, and to some stretch techniques used with physical therapy. [ABSTRACT FROM AUTHOR]

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 fibroblast's 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. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: The scientific basis for acupuncture meridians is unknown. Past studies have suggested that acupuncture meridians are physiologically characterized by low electrical impedance and anatomically associated with connective tissue planes. We are interested in seeing whether acupuncture meridians are associated with lower electrical impedance and whether ultrasound-derived measures - specifically echogenic collagenous bands - can account for these impedance differences. Methods/Results: In 28 healthy subjects, we assessed electrical impedance of skin and underlying subcutaneous connective tissue using a four needle-electrode approach. The impedances were obtained at 10 kHz and 100 kHz frequencies and at three body sites - upper arm (Large Intestine meridian), thigh (Liver), and lower leg (Bladder). Meridian locations were determined by acupuncturists. Ultrasound images were obtained to characterize the anatomical features at each measured site. We found significantly reduced electrical impedance at the Large Intestine meridian compared to adjacent control for both frequencies. No significant decrease in impedance was found at the Liver or Bladder meridian. Greater subcutaneous echogenic densities were significantly associated with reduced impedances in both within-site (meridian vs. adjacent control) and between-site (arm vs. thigh vs. lower leg) analyses. This relationship remained significant in multivariable analyses which also accounted for gender, needle penetration depth, subcutaneous layer thickness, and other ultrasoundderived measures. Conclusion/Significance: Collagenous bands, represented by increased ultrasound echogenicity, are significantly associated with lower electrical impedance and may account for reduced impedances previously reported at acupuncture meridians. This finding may provide important insights into the nature of acupuncture meridians and the relevance of collagen in bioelectrical measurements. [ABSTRACT FROM AUTHOR]