PROJECT SUMMARY Myofascial pain syndrome (MPS) is one of the most common forms of acute and chronic musculoskeletal pain, a common cause for opioid use, and affects 10-15% of patients seen in general medical clinics. Central to this syndrome are myofascial trigger points (MTrPs), hard, palpable, discrete, and localized nodules that produce referred pain and local tenderness at the site upon compression. Despite its prevalence and clinical significance, the pathophysiology of MPS is not well understood. The subjective nature of current diagnostic methods and a lack of objective markers of MPS, hinders the precision of diagnosis and treatment. There is therefore a clinical need for improved diagnostic tools sensitive to the complex multifactorial (compositional, vascular and neurogenic) factors of MPS, that can unravel the intricate mechanisms of MPS and enhance patient care. Imaging offers objective measures of multiple disease features to improve the diagnosis and assessment of MTrPs and MPS. MRI, with its excellent soft-tissue contrast, can provide detailed anatomical information of skeletal muscle and fascia. Further, quantitative methods can probe muscle microstructure [Diffusion Tensor Imaging (DTI) and Diffusion Kurtosis Imaging (DKI)], microcirculatory velocity [Intravoxel Incoherent Motion (IVIM)], local contraction (dynamic Diffusion Weighted Imaging), muscle and fascial fibrosis and densification [Ultra-Short Echo Time (UTE) MRI]. Synergistically, PET imaging, with its sensitivity to functional and metabolic process, provides a tool for assessment of inflammatory processes including neurogenic inflammation. This work aims to develop PET and MRI methods to identify novel imaging biomarkers that can diagnose and characterize MTrPs in MPS. Our Specific Aims are (1) develop clinically-translatable [18F]FDG PET-MRI imaging markers that can reflect disease and pain mechanisms and characterize MTrPs in MPS; (2) evaluate whether PET and MRI biomarkers are able to differentiate the microstructural, compositional, functional and metabolic changes in MPS patients from normal myofascial and neurogenic features in age and sex matched controls as between MPS patients with pain in their upper back muscles (Trapezius, Rhomboid Major an Minor, and Levator Scapulae) and the same muscles on their non-painful contralateral side. If successful, based on an receiver operator characteristics (ROC) area under the curve (AUC) of 0.7, we will (3) evaluate our imaging approaches in a single-blind randomized clinical trial of patients being treated with ultrasound guided muscle anesthetic injections and a sham injection to evaluate treatment response and differences between treatment groups. The significance of our work is the development of novel biomarkers that can objectively diagnosis and characterize tissue level changes in MTrPs and MPS . Our key innovation is the development of PET and MRI tools to assess specific mechanisms of theorized MPS and MTrPs pathophysiology as well as mechanisms of pain generation in MPS. Our investigative team includes experts in novel imaging techniques, clinical assessment and treatment of pain, and clinical studies evaluating both imaging markers and treatment response.

NARRATIVE Myofascial pain syndrome (MPS), characterized by the presence of painful myofascial “trigger points”, is one of the most common forms of acute and chronic musculoskeletal pain, affecting 10-15% of patients seen in general medical clinics and as many as 85% of individuals at some point in their lifetime. Despite its clinical significance, the subjective nature of current diagnostic methods, together with the lack of objective markers of MPS, has hinders the precision of MPS diagnosis and treatment. This work aims to develop PET and MRI methods to identify novel imaging biomarkers of myofascial damage and the resultant inflammatory mediators that can diagnose and characterize MTrPs and the sources of pain in MPS.