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Underlying Mechanisms of Force-based Manipulations: High-Priority Research Networks

Project Concept Review

Council Date: February 7, 2020

Program Officer: Merav Sabri, Ph.D.


Force-based manipulations refer to the passive application of mechanical force to the outside of the body with therapeutic intent, rather than active movement or exercise. Examples of force-based manipulations include light touch, pressure, thrust, and needling. The range of applied forces in manipulations is diverse. The forces applied in spinal manipulation are about 1,000 times greater than those in acupuncture needling, and the forces in massage are intermediate between these two.  Tissues may respond to different forces—or, more accurately, to the stresses and strains they induce.  Currently, fundamental understanding of the mechanisms by which force-based manipulations exert their effects is lacking. In the field of neuroscience, a large body of research has focused on understanding the neural systems involved in force-based mechanosensation. However, scientists in this field have been completely unaware of the relevance of their work to the science behind manual therapies, such as massage and chiropractic.

In September 2019, the National Center for Complementary and Integrative Health (NCCIH) and the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD)/National Center for Medical Rehabilitation Research (NCMRR), in collaboration with the National Institute of Neurological Disorders and Stroke (NINDS) and other NIH institutes (National Institute of Biomedical Imaging and Bioengineering [NIBIB]; National Institute on Aging [NIA]), sponsored a roundtable discussion with the following goals: 

  • Identify research gaps and barriers in the field of force-based manipulations
  • Discuss new research opportunities in this field
  • Promote collaborations among neuroscientists, manual therapists, physiologists, mathematicians, and engineers to advance cutting-edge research related to force-based manipulations
  • Develop and encourage the use of common terminology.

The roundtable participants presented and discussed the following topics: Defining biomechanical force; peripheral neural and extraneural sensing of biomechanical force; spinal cord transmission of force sensation; central processing and modulation of biomechanical force; and technology advances for force-based manipulations.

Through workshop presentations and discussion, research gaps and opportunities were noted that included a need to: 1) characterize and quantify the types of forces; 2) develop reliable measures of force/stress/strain/stiffness; 3) identify metrics and biomarkers for short/long term therapeutic responses; 4) develop methodologies for applying and quantifying forces (e.g., robotics, simulation programs); 5) develop technologies for real-time recording and imaging of cells and tissues during force-based manipulations; 6) define and quantify psychosocial and expectation effects relevant for force-based manipulations; 7) link therapy to multiscale response, i.e., knowledge of the molecular, cellular, and circuit mechanisms that underlie the effects of various manual therapies; 8) develop opportunities to connect neuroscientists, engineers, and clinicians-scientists.

Purpose of Proposed Initiative

This proposed initiative aims to solicit applications that focus on developing resources by refining and testing key concepts that will advance and further support the study of the neural circuitry of force-based manipulations.  This grant funding initiative will support research networks through meetings, conferences, small-scale pilot research, multidisciplinary cross training (such as intensive workshops, summer institutes, or visiting scholar programs), and information dissemination to foster the growth and development of research in the specified priority areas listed below. 


The scientific scope of networks is limited to the following high-priority research areas:

  1. Terminology and measurement of force-based manipulations: Develop common terminology and metrics to characterize, uniformly define, and quantify the types of mechanical force (applied in various manual therapies, such as physiotherapy, chiropractic, light/deep massage therapy, etc.).  Develop and validate objective measures of force, stress, strain, stiffness and the response to force at multiple levels of analysis (cellular, molecular, extraneural and neural, behavioral, psychological, and social), their interrelations, and/or their variation across the lifespan and diverse population subgroups (e.g., chronic pain patients).
  2. Mechanistic research on the neural circuitry of force-based manipulations: Identify and examine neural circuits involved in force-based manipulations. 
  3. Contextual effects of force-based manipulations: Define and quantify external influences such as psychosocial, affect/mood, and expectation effects on various neural circuits of force-based manipulations.
  4. Biomarkers of force-based manipulations: Identify biomarkers for short- and long-term therapeutic responses to forced-based manipulations in the context of appropriate human and animal models (e.g., low-back pain, myofascial pain syndrome).
  5. Technology and methodology development for mechanistic studies: Identify/adapt/develop methodologies for applying and quantifying forces (e.g., robotics, simulation programs, virtual reality). Develop technologies for real-time recording and imaging of cells and deep tissue during force-based manipulations. Develop computational mechanistic models that include, historical factors, social factors, and affect/mood.