Summary/Abstract Myofascial pain syndrome (MPS) is highly prevalent in the community. It is primarily diagnosed using patient self reports and physical examination, which lack reliability, sensitivity and specificity and does not provide insights into the abnormal biological and physiological processes in soft tissues. While a number of treatment methods are available to patients, there are currently no criteria to determine which treatments might be best for each patient’s unique myofascial pain phenotype. To improve evidence-based management of myofascial pain, there is a critical need to develop quantitative measures that advance our understanding of the physiological processes in the underlying the soft tissues across the clinical continuum of MPS. The objective of this project is to develop a quantitative biomarker informed by the current understanding of underlying tissue-level mechanisms at the level of the “myofascial unit” (muscle, nerve, fascia, vasculature, lymphatics) that are likely to be involved in MPS. This project has two phases: a R61 phase for developing and validating the biomarker and an R33 phase for utilizing the biomarker for treatment monitoring in a randomized clinical trial of two different mechanism-based interventions. The R61 phase has two specific aims: Specific Aim 1: Develop and refine quantitative measures of muscle, fascia, interstitium and blood flow and determine reproducibility. The measures will be based on quantifying three physiological mechanisms: (1) Aim 1a: impaired myofascial gliding quantified through measures of shear anisotropy using ultrasound shear wave elastography; (2) Aim 1b: abnormal accumulation of interstitial fluid and impaired perfusion quantified through ultrasound elastography, Doppler ultrasound and bioimpedance spectroscopy; (3) Aim 1c: increased motor unit excitability associated with segmental sensitization quantified through high-density surface electromyography. Specific Aim 2: Develop and clinically validate a composite classifier of myofascial state. We will measure the tissue-level biomarkers in a longitudinal observational study of patients with myofascial pain and pain-free controls. The classifier will be designed to predict clinical phenotypes that include within subject variability over time, as well as variability between subjects with myofascial pain and controls. The transition criteria from the R61 to R33 phase will be achieving >90% classification accuracy using a classifier based on tissue-level biomarkers to differentiate between normal, latent, and active phases. Our objective in the R33 phase is to determine the sensitivity and specificity of the composite classifier to predict treatment response. To evaluate whether the composite measure is sensitive to mechanism-based changes, we will evaluate two interventions that target two different mechanistic pathways: dry needling targeting segmental sensitization, and hyaluronidase injections targeting impaired fascial gliding. We will conduct a randomized, placebo-controlled double-blind clinical trial of the two interventions using a factorial design.

Project Narrative This project seeks to develop and validate a quantitative biomarker that enables the differentiation between normal physiological processes in soft tissues such as muscle, connective tissue, nerve, blood vessels and extracellular fluid, and pathological processes in these tissues that may be associated with myofascial pain syndrome. The successful completion of this project is expected lead to improved criteria for diagnosis and non- pharmaceutical management of myofascial pain, which is widely prevalent in the community.