ABSTRACT / PROJECT SUMMARY
The goal of this proposal is to establish a high-priority research network to identify mechanisms through which
soft tissue manipulation (STM), such as massage, exerts biological effects on the nervous system, non-neural
cells and tissues. Neuromusculoskeletal pain afflicts up to half of the adult U.S. population and is the most
commonly cited health reason for receiving massage. Soft tissue manipulation has been shown to promote
relaxation, reduce anxiety, attenuate pain, mitigate inflammation, and promote functional change. STM also
offers non-addictive alternatives to pharmacological interventions for short-term pain relief. Although STM has
been used widely since ancient times, the underlying mechanisms of STM’s beneficial effects are not well
understood, and STM interventions are not optimized based on rigorous and compelling scientific evidence.
Although mechanistic studies over the past decade have identified molecular, cellular and circuit mechanisms of
discriminative touch sensation in mammals, how these neural pathways are engaged by STM is unknown.
Moreover, the cells and circuits that mediate affective components of touch sensation have not been defined.
To enable mechanistic research into therapeutic effects of STM, interdisciplinary research and new resources
are needed. The field requires collaboration between manual therapists, neuroscientists, engineers, and cell
biologists. Scientific conferences or other networking opportunities that bridge these disciplines do not currently
exist. This application in response to RFA-AT-21-006 will create a cross-disciplinary research network of
scientists and clinicians with the shared goal of developing technologies and collaborations to break barriers to
progress. First, few quantifiable standards exist to rigorously measure either how therapists apply hands-on
manipulations, or how these manipulations alter stress/strain fields in receiving tissues. Second, the field lacks
technologies and computational models to quantify the spatiotemporal dynamics of STM techniques. Third, how
non-neural signals and cell types, including cytokines, immune cells, fibroblasts, and epithelial cells, promote
restorative repair versus fibrotic healing have not been defined. Our core investigative team consists of scientists
and clinicians whose collective expertise spans physical therapy, neuroscience from molecules to circuits in the
mouse and human nervous systems, engineering and tissue mechanics, and extraneural tissues including the
immune, myofascial and integumentary systems. To advance mechanistic research on STM and
mechanosensory signaling, the U24 network aims to 1) Organize a Conferences Program to promote inclusive
networking and cross-disciplinary collaborations, draw diverse researchers and clinicians to the field, and foster
mechanistic, multi-scale research on the neurobiology of mechanotherapy. 2) Implement a Pilot Project Program
to generate new tools for quantifying force-based manipulations, testable hypotheses, and new mechanistic
knowledge. 3) Rapidly and freely disseminate high-impact research to advance the field by sharing innovative
concepts and technologies that define neural mechanisms of the beneficial effects of STM.