Key Dates

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National Center for Complementary and Integrative Health (NCCIH)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute of Neurological Disorders and Stroke (NINDS)

The National Institutes of Health (NIH) intends to publish one Funding Opportunity Announcement (FOA) to solicit applications on the development of innovative quantitative imaging and other relevant biomarkers of myofascial tissues for pain management in human subjects using a two-phase grant funding mechanism. Candidates for such biomarkers may include objective measures based on minimally invasive imaging technologies, electrophysiological recordings, integration of multiparametric imaging and electrophysiological approaches, or their integration with other markers (e.g., immune factors, genomic markers, physiological factors, etc.) through multiscale modeling or machine learning analysis. The first phase of the award will provide funding for up to 2 years to develop quantitative measures that can differentiate myofascial tissue abnormalities in healthy, versus latent, versus active myofascial pain stages using cross-sectional correlations with clinical signs/symptoms. The second phase will provide up to 3 years of support to assess the ability of the measures developed in Phase 1 to monitor responses and/or predict outcomes in response to specified therapies to relieve myofascial pain in longitudinal interventional studies. Transition between the two phases of the award will be administratively reviewed and will be determined by successful completion of quantifiable “transition milestones” that need to be clearly specified in the application.

The purpose of this notice is to allow potential applicants sufficient time to develop meaningful collaborations among technology developers, myofascial tissue experts, pain researchers, and clinicians. It will also allow potential applicants sufficient time to develop responsive projects to the two-phased FOA. The FOA is expected to be published in Fall2021, with an expected application due date in Winter2021. Details of the planned FOA are provided below.

This effort is part of the NIH HEAL (Helping to End Addiction Long-term^SM) Initiative to speed the development and implementation of scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative^SM will bolster research across NIH to (1) improve treatment and prevention of opioid misuse and opioid use disorder and (2) enhance pain management. More information and periodic updates about the Initiative are available at: https://heal.nih.gov/.

Myofascial pain, pain originating from muscles and/or associated soft tissues such as fascia, is likely an important component of many severe and chronic pain conditions, including chronic low back pain, temporomandibular disorders, chronic neck and shoulder pain, as well as headache.However, knowledge regarding the contribution of myofascial tissues—especially fascia and the interactions between fascia, muscles, and peripheral nerves—to many pain types remains mostly scant. Consequently, evidence on which treatments are effective for myofascial pain is limited, and clinicians currently lack objective guidance on how to treat pain conditions with myofascial origin. Thus, identifying and developing quantitativeand innovativebiomarkers for myofascial tissues are critical for effective pain management regimes through a variety of therapeutic approaches, including nonpharmacologic therapies. In addition, such biomarkers may also shed light on the transition from acute to chronic pain.

In 2020, HEAL funded a workshop on “Quantitative Evaluation of Myofascial Tissues: Potential Impact on Musculoskeletal Pain Research,” which pointed to a unique and transformative research opportunity for HEAL to combat the challenges of pain management and opioid addiction. The video recordings (Day 1 and Day 2), executive summary, and detailed summary of the workshop can be found here: https://www.nccih.nih.gov/news/events/nih-heal-initiative-workshop-on-myofascial-pain.

This Notice encourages investigators with expertise, insights, and interests in this area of developing quantitative imaging biomarkers of myofascial tissues for clinical pain management to begin to consider applying for this new FOA.

Collaborative investigations combining expertise in minimally invasive imaging technology, quantitative analysis and computational modeling, myofascial pain, and nonpharmacologic or integrative pain management will be encouraged, and these investigators should also begin considering applying for this new FOA.

Among the areas of research encouraged in this initiative are pain conditions involving myofascial tissues. Examples include musculoskeletal pain such as chronic low-back pain, temporomandibular disorders, chronic neck and shoulder pain, as well as other types of painful conditions such as headache and migraine.

Research Objectives

There are two main objectives to be achieved in the two-phased FOA.

Objective 1 (Phase 1): Observational Studies

The primary objective of the first phase is to identify and develop quantitative measures,which can differentiate myofascial tissue abnormalities in healthy, versus latent, versus active pain stages in humans via observational studies and cross-sectional correlations with clinical signs/symptoms.

Examples of quantitative technologies for Phase 1 studies may include:

1. Structural imaging (e.g., magnetic resonance [MR], ultrasound), addressing improved spatial resolution needed to visualize microstructures such as muscle spindles that may be involved in myofascial pain
2. Functional assessments (e.g., elastography) to quantify soft tissue mobility and biomechanical properties (e.g., stiffness, viscosity, shear plane mobility)
3. Quantitative evaluation of tissue metabolism, perfusion, pH, oxygenation, and fatty infiltration (e.g., PET (positron emission tomography), optical, photoacoustic, MR spectroscopic imaging, electrophysiological measurements of muscle, sensory, motor, and autonomic peripheral activity)
4. Multimodal, multiparametric, and multiscale approaches integrating different types ofmeasurements, including dynamic changes in tissue targets

Investigators are encouraged to choose one or multiple types of technologies described above to develop the quantitative measures to assess the "myofascial unit", including muscles and associated connective tissues, nerves, blood vessels, and lymphatics.

Objective 2 (Phase 2): Interventional Studies

The primary objective of the second phase is to build on the quantitative measures identified and developed in Phase 1 to develop biomarkers and test their abilities to monitor responses and predict pain related outcomes, including patient-reported outcomes, in response to one or a combination of treatments or therapies specified below in randomized and controlled longitudinal interventional studies of patients with pain.

Applicants are encouraged to choose one or more of the following treatments or therapies for the Phase 2 study:

1. Physical force-based manipulations, such as manual therapies (e.g., massage therapy, soft tissue mobilization, strain-counterstrain techniques, joint mobilization, muscle energy techniques, high velocity/low amplitude thrusting, spinal manipulation, osteopathic manipulation, gua sha) and stretching-based physical activities (e.g., yoga, tai chi, dance therapy)
2. Dry needling or acupuncture
3. Thermotherapies (e.g., heating, or cooling/cryotherapy)
4. Local chemical-based injection therapies (e.g., lidocaine injection therapy)

HEAL Initiative

This study will be part of the of the NIH HEAL (Helping to End Addiction Long-term^SM) Initiative to speed the development and implementation of scientific solutions to the national opioid public health crisis. HEAL will bolster research across NIH to (1) improve treatment and prevention of opioid misuse and opioid use disorder and (2) enhance pain management. More information and periodic updates about the Initiative are available at: https://heal.nih.gov/.

Applications are not being solicited at this time. 

Please direct all inquiries to:

Wen G. Chen, Ph.D.

National Center for Complementary and Integrative Health (NCCIH)

301-451-3989

chenw@mail.nih.gov

Guoying Liu, Ph.D.
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
301-594-5220
Email: liug@mail.nih.gov

Merav Sabri, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
301-496-2583
Email: merav.sabri@nih.gov