Concept: Quantitative Evaluations of Myofascial Tissues: Potential Impact on Musculoskeletal Pain Research

Project Concept Review

Council Date: February 7, 2020

Program Officer: Wen G. Chen, Ph.D., and Merav Sabri, Ph.D.

Background

Myofascial pain syndrome (MPS), pain originating from muscles and/or associated soft tissues such as fascia, is estimated to affect 30 to 85 percent of patients with musculoskeletal pain. MPS may be the origin of many severe and chronic pain conditions, including chronic low-back pain, temporomandibular disorders, chronic head and shoulder pain, as well as headache. Like most pain conditions, MPS may be largely managed by standard nonopioid therapies and treatments. For a fraction of these patients, however, the standard therapies are not sufficient and opioid-based therapies are often used instead. The field of musculoskeletal pain so far has largely focused on the skeletal (bones, joints, intervertebral discs) and central nervous system (CNS) contributions, whereas the myofascial components, especially the fascia component as well as the interactions between fascia and muscles, remain mostly unknown. At the same time, many chronic musculoskeletal pain patients don’t respond to surgery (targeting the skeletal part) or develop significant side effects to opioids (targeting the CNS) or both. Therefore, there is a strong need to address the contributions of the myofascial tissues to chronic pain as they are among the last “unturned stones” of all the tissue types involved in musculoskeletal pain.  

Currently, MPS is clinically diagnosed by the palpation of tender, indurated foci termed myofascial “trigger points” that are associated with spontaneous local and/or radiating pain. An important current limitation in musculoskeletal pain research is that diagnostic imaging of soft tissues lags far behind that of specialized tissues such as bone and cartilage. However, there is increasing awareness that musculoskeletal pain pathophysiology is complex and can involve “soft” tissues including muscles, fasciae, and other nonspecialized connective tissues. MPS is distinct from fibromyalgia, which is a CNS disorder characterized by diffusely increased pain sensitivity, with comorbid sleep disturbance, depression, and functional disturbances in other organ systems such as irritable bowel syndrome. In contrast, MPS is clinically diagnosed by the palpation of tender, indurated foci termed myofascial “trigger points” that are associated with spontaneous local and/or radiating pain. There is no available objective method to diagnose these palpable lesions. 

Although various types of nonpharmacologic treatments are used empirically to treat MPS, none has been validated, or even tested under controlled conditions, and MPS is largely missing from the portfolio of studies funded (to date) by the HEAL initiative. One explanation for this paradox is that MPS is currently a clinical diagnosis based on history and physical examination, and there are no objective methods to 1) confirm the diagnosis, 2) evaluate effectiveness of treatments, and 3) follow patients over time. This lack of diagnostic methods has prevented the field of MPS research from developing, and constitutes an important gap, not only in the HEAL initiative, but in NIH pain research as a whole.  

Purpose of Proposed Initiative 

There is, therefore, a need for improved quantitative evaluations, such as imaging, biopsies, and electromyography recording, of muscles and fasciae to advance research on the pathophysiology and treatment of MPS.  Furthermore, structural imaging alone is not sufficient—an understanding of pathophysiological processes must involve functional imaging that can measure local increases in tissue stiffness and reveal how musculoskeletal tissues behave during movement. In particular, we need better methods to objectively measure the loss of mobility between adjacent fascia layers that can occur due to chronic inflammation, fibrosis, and adhesions, and may predispose to the development of MPS lesions. Techniques such as ultrasound and magnetic resonance (MR) elastography have shown early promise in musculoskeletal tissue applications but are not currently optimized for implementation in clinical trials.  

Examples of basic needs for improved myofascial pain assessment and treatments include: 

1. Improved CT and MR methods for structural imaging to address current limitations in settings to visualize muscles, fasciae and nonspecialized connective tissues. In particular, improved spatial resolution is needed in CT and MRI to visualize structures, such as muscle spindles, that may be involved in MPS.  
2. Development and validation of functional evaluations, including imaging methods, to quantify soft tissue mobility and biomechanical properties (e.g., stiffness, viscosity) in response to a standardized mechanical input. As for structural imaging, these techniques need to have sufficient resolution to measure shear plane motion between adjacent fascial planes, and the loose connective tissue interfaces that separate them.  
3. Imaging techniques need to be applicable to different body regions including the upper and lower back, neck, shoulders, and temporomandibular areas.

Improved objective assessments such as imaging, biopsy, and/or electrophysiological recordings of tissues involved in MPS will be an important step toward incorporating soft tissues into the phenotyping of patients with “nonspecific” musculoskeletal pain. More generally, while substantial efforts are aimed at understanding neurophysiological mechanisms in chronic pain, it is important to also investigate structural, metabolic, and biomechanical mechanisms involving soft tissues that could contribute to the functional impairments that occur with musculoskeletal pain. Importantly, these functional impairments can themselves contribute to further tissue deterioration, and this process may be reversible with nonopioid treatments that restore function.

Objectives

This concept initiative builds on the HEAL-approved FY 2020 Workshop on “Quantitative Evaluations of Myofascial Tissues: Potential Impact on Musculoskeletal Pain Research.” This workshop will bring together clinical research experts in diagnosis and treatment of musculoskeletal painful conditions, imaging, biotechnology, and biomechanics, as well as computational modelers to discuss cutting edge research related to the development or improvement of imaging and other quantitative technologies that would allow diagnosis and quantification of the pathophysiology, as well as identification of hallmarks manifested in MPS. We propose to follow up the workshop with an initiative. The goal of this proposed initiative would be to develop and evaluate methodologies/technologies (such as imaging) that would allow quantitative evaluation of musculoskeletal pathophysiology as well as identification of objective diagnostic and prognostic hallmarks manifested in MPS. In turn this could advance clinical trials of innovative individualized nonopioid therapies for this condition. We are proposing a phased approach as described below.   

Phase 1: Technology development and validation

Currently the diagnosis of MPS is made by palpation of soft tissue lesions that are 1) tender to palpation and 2) feel stiff compared with surrounding tissue. The goals of the first phase of this research will be to: 

1. Assemble a team of clinicians with expertise in myofascial pain and assess intra- and inter-rater reliability in detecting myofascial lesions by palpation in different body areas (e.g., neck/shoulders/upper back, low back, temporomandibular area). 
2. Evaluate the ability of existing technology (e.g., ultrasound, MRI, elastography) to visualize and measure lesion volume and/or detect differences in tissue stiffness compared with surrounding tissues, for lesions that can be reliably detected by palpation.
3. Refine and further develop imaging techniques to improve image resolution.  
4. Iterate this process until image detection achieves acceptable sensitivity and specificity. 
5. Evaluate test-retest stability of measurements over time (days to weeks) without treatment. 

Phase 2: Testing of nonpharmacologic treatments and other nonaddictive therapies

Current empirical treatment of MPS includes acupuncture or “dry needling,” injections (lidocaine or D5W), and manual therapies. The goals of the second phase will be to test the effects of these treatments using imaging measurements as biomarkers:

1. Patients with MPS symptoms and measurable lesions randomized to treatment vs. control (sham or waitlist).
2. Repeat imaging measurements and symptoms assessment over time (e.g., days, weeks).
3. Assess correlation between change in tissue measurements and change in symptoms.