The critical need, importance, and value of mechanistic Force-Based Manipulations research

Identifying the physiological mechanisms of Force-Based Manipulations (FBM) (also known as manual therapy) is critical to the advancement of the field, as well as to the clinical optimization of any therapeutic FBM intervention. By definition, FBM mechanisms reflect the active processes and/or components of treatments and how they result in positive clinical outcomes. The difficult task of performing mechanistic-oriented FBM research must be undertaken with a much greater urgency by multidisciplinary teams of investigators if we are to succeed in identifying the essential, unique, and/or shared mechanisms of FBM interventions. Intentional and mechanistic-focused FBM research efforts are needed to address unanswered questions related to FBM dosage, identifying clinical subpopulations who will benefit from FBM, and identifying key FBM moderators. Delays in addressing these critical questions will continue to thwart the advancement of the FBM field, retarding the development of new and optimized forms of manual therapy.

In September 2019, a National Institutes of Health ‘Neurocircuitry of Force-Based Manipulations Workshop’ [1] was organized by the National Center for Complementary and Integrative Health (NCCIH) and the National Institute of Neurological Disorders and Stroke (NINDS) to highlight the current knowledge of biological mechanisms of force sensing and biomechanical Force-Based Manipulations. The workshop identified several critical FBM knowledge gaps (Table 1).

Table 1. Gaps in Force-Based Manipulations (FBM) knowledge.

Determining the types of FBM biomechanical forces that impact neural and nonneural cells, and how are these involved in FBM therapeutic responses

Identifying spinal, brainstem, cortical circuits (micro/macro scale) involved in processing FBM-related inputs

Determining mechanoreceptor and neural circuitry response to FBM-related treatment in pathological or inflammatory/painful conditions

Determining the impact of superficial and deep tissue mechanics in real time during and after FBM delivery. The amount of tissue deformation occurring due to FBM and whether certain tissues primarily respond to stress or strain, while defining the role that fibrosis and tissue stiffness changes play in FBM physiological response and/or therapeutic outcomes

Quantifying internal loads in relation to external FBM load application and kinematics

Defining the role of mechanosensitive ion activity (i.e. TRAAK, TREK1, TREK2, Piezo1, Piezo2) in relation to FBM delivery

Defining the contribution of neurotransmitters (i.e. pain-related neuropeptides), integrins, endogenous opioid, and primary afferent muscle spindle response to FBM and their relationship to clinical outcomes

Developing biophysically realistic computational models related to FBM treatment and/or pain signaling

Defining the contribution and importance of contextual factors to FBM clinical outcomes

The workshop also identified long-standing FBM scientific and professional barriers (Table 2) that should be successfully dismantled.

Table 2. Force-Based Manipulation (FBM) barriers.

A poorly defined, often inaccurate, and/or nonscientific FBM terminology commonly used in clinical and/or basic publications between different FBM professions, clinicians of the same FBM profession, and/or scientists/basic science researchers

A lack of reliable and objective measures of force and biometrics for subcutaneous and deep tissues

A much greater understanding of the psychosocial factors among clinicians delivering FBM and between patients receiving FBM

A lack of understanding of unique and shared contextual factor contributions across all FBM interventions and their relationship towards mild-to-moderate FBM clinical efficacy

A lack of more clinically relevant animal pain models that mimic much more closely clinical FBM treatment as opposed to more generalized sensory stimulation. Genetic models other than mice and the use of larger animals (porcine or ovine) would prove useful in providing FBM treatment that more closely resembles clinical FBM delivery and real-time in vivo tissue response

A lack of adequate computational models that include multi-physics and account for the large variance among clinical delivery parameters of FBM (i.e. massage) so as to mirror real-world clinical settings

A lack of sustained lines of FBM scientific investigation, and sustained collaborations between FBM clinicians and Tier-1 research intensive academic institution multi-disciplinary investigators

A lack of an adequate academic research FBM workforce with a need for greater federal research support and FBM career development training opportunities

This FBM mechanistic research challenge is formidable to say the least, but the goals outlined above are tractable, as the science and technology required to successfully overcome many, if not all, of the aforementioned barriers are available to the research community. However, success will require abandoning previous dogma and silos, approaching the necessary research with an open mind and a willingness by researchers/clinicians to establish multidisciplinary collaborations with both basic and clinical researchers outside of their particular FBM profession. As part of a NIH sponsored U24 initiative, the leadership team of ForceNET [2] endeavors to bridge the knowledge gap between research in force-based mechanisms and outcomes relevant to patients and their clinicians. This sponsored special issue in JMMT is the first of many steps that ForceNET plans to take along with our fellow U24 sponsored networks (SpineWork [3] and Neurons_MaTTR [4]) to better identify FBM-related mechanisms and advance the FBM field.

Acknowledgements

This work was funded by the National Institutes of Health/National Center for Complementary and Integrative Health (NCCIH) and the National Institute of Neurological Disorders and Stroke (NINDS), U24AT011969 to WRR and CC.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Notes on contributors

William R. Reed

William R. Reed, DC, PhD, is an Associate Professor in the Physical Therapy Department and the Director of the Rehabilitation Science Program at the University of Alabama at Birmingham. Dr. Reed’s background is as a manual therapy clinician (chiropractor) who after 14 years left private practice to pursue a research career investigating physiological mechanisms underlying manual therapy and physical rehabilitation approaches aimed at alleviating musculoskeletal pain. He has received multiple NIH awards to investigate the effects of spinal joint dysfunction on lumbar muscle spindle primary afferent discharge during spinal manipulation in animal models. He has worked to characterize muscular low back pain in various animal models to investigate mechanisms responsible for musculoskeletal pain relief related to manual therapy interventions and has over 60 publications in peer-reviewed scientific journals. He currently serves as MPI with Dr. Chad Cook (Duke) on a NIH U24 award to develop a sustainable research network called ForceNET (https://sites.duke.edu/forcenet/) aimed at developing interdisciplinary collaborations to address current mechanistic knowledge gaps and successfully overcome long-standing barriers in the field of manual therapy.

Chad Cook

Chad Cook, PT, PhD, MBA, FAPTA is a professor at Duke University, where his primary appointment is in the Department of Orthopaedics; he has secondary appointments in the Department of Population Health Sciences and the Duke Clinical Research Institute. He is part of over 11 million dollars in external funding and is a prolific researcher with over 360 publications.

Vitaly Napadow

Vitaly Napadow, PhD, LicAC, is Professor of Physical Medicine and Rehabilitation, as well as Radiology, at Harvard Medical School. He is also the Director of the Scott Schoen and Nancy Adams Discovery Center for Recovery from Chronic Pain at Spaulding Rehabilitation Hospital and the Center for Integrative Pain Neuroimaging (CiPNI) at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital. Vitaly has been a pain neuroimaging researcher for more than 20 years and holds a clinical acupuncture practice at the Pain Management Center of Brigham and Women’s Hospital. Dr. Napadow’s neuroimaging research seeks to reveal mechanisms by which different brain circuitries modulate pain perception and to better understand how non-pharmacological therapies, from acupuncture to spinal manipulation, ameliorate chronic pain. Dr. Napadow has served as PI on numerous R01 and P01 level grants and has more than 220 publications in leading peer-reviewed scientific journals. He is past-President of the Society for Acupuncture Research, and serves on the board of the US Association for the Study of Pain (USASP) and numerous conference, journal, and NIH review panels.

Dawn M. Elliott

Dawn M. Elliott, PhD, is the Blue and Gold Professor of Biomedical Engineering at the University of Delaware. She is the director of the NIH-funded Delaware Center for Musculoskeletal Research. Dr. Elliott was the founding chair of the BME department at Delaware from 2011-2020. Prior to joining Delaware, she spent 12 years in the University of Pennsylvania’s Departments of Orthopaedic Surgery and Bioengineering. Dr. Elliott’s group studies damage and treatment of orthopaedic tissues including disc, meniscus, and tendon. Her research approach integrates mechanical testing, mathematical modeling, and multi-modal imaging across multi-scales, from the entire joint-level, to the tissue- and the micro-scale.

Greg Kawchuk

Dr. Greg Kawchuk, BSc, DC, MSc, PhD, is a full professor in the Faculty of Rehabilitation Medicine in the Department of Physical Therapy at the University of Alberta. Greg is a Canadian Memorial Chiropractic College graduate (1990) who practiced chiropractic for 15 years in multidisciplinary settings before earning his PhD in bioengineering and becoming a full-time researcher. He was the recipient of the first chiropractic research chair in Canada and in 2004, was recruited to the University of Alberta as the Canada Research Chair in Spinal Function. Dr. Kawchuk’s research interests are focused on back pain and spine function. His work spans basic science, clinical trials and implementation. Competitive awards from major provincial, national and international funding agencies support Dr. Kawchuk’s work and include CIHR, NSERC, and NIH. To date, his work has resulted in over 150 papers, the most recent of which have been published in Scientific Reports and PLOS One. Dr. Kawchuk is a founding member of CARL, the Chiropractic Academy for Research Leadership, a global mentoring program for early-career scientists and is presently leading the new GLA:D Back initiative in Canada.