Background & Aims

Chronic low back pain (CLBP) is a leading determinant of disability worldwide, and the cause of enormous health care expenditures. Fibromyalgia (FM) is a chronic pain condition characterized by widespread pain that is not explained by tissue lesions. Current treatments are of modest efficacy in both conditions, and opioids remain commonly prescribed. Because we know very little about the molecular mechanisms promoting CLBP and FM, we are unable to target them. Furthermore, no biomarkers that support precision medicine for these conditions are available. We aim to identify molecular pathways potentially involved in the pathophysiology of CLBP and FM by applying a multiomic approach (metabolomics, lipidomics, proteomics, and cytokines) in thoroughly phenotyped patients attending the Center for Pain Relief at the University of Washington. We aim to discover molecular pathways promoting CLBP and FM that would shift the focus of research to the development of candidate biomarkers and target

Methods

We will study 100 patients with CLBP, 100 with FM, and 200 pain-free controls. Phenotyping characteristics include demographics, pain intensity, Widespread Pain Index and Symptom Severity Scale, pressure pain thresholds, PROMIS Physical Function 4-item short form, neuropathic components using quantitative sensory test and the DN4 questionnaire, and pain facilitation (temporal summation). Patient sex and measures of psychosocial function will be analyzed as moderators: depression (PHQ-2), anxiety (GAD-2), and catastrophizing (4-item Pain Catastrophizing Scale). Metabolomics and lipidomics analysis will include global and targeted metabolite profiling of aqueous metabolites, lipids, and oxylipin signaling lipids. Proteomics will include MS-based Discovery Proteomics. Cytokines will include a multiplexed analyte panel. We will compare blood and urine in the three groups and associate multiomic profiles with the above phenotyping characteristics.

Results

Recruitment and enrollment procedures have begun, data is being collected.

Conclusions

The study can lead to the identification of novel therapeutic targets for CLBP and FM, and of candidate biomarkers with high clinical implementation potential. The extensive phenotyping can allow the identification of phenotype-specific therapeutic targets and biomarkers. The study of a regional (CLBP) and a widespread (FM) musculoskeletal pain syndrome will allow us to identify pathways that are common or specific to one of the two conditions.

References

N/A.

Presenting Author

Abby P. Chiu

Poster Authors

Michele Curatolo

MD, PhD

University of Washington

Lead Author

Abby Chiu

University of Washington

Lead Author

Catherine Chia

Lead Author

Ava Ward

Lead Author

Sandra K. Johnston

Lead Author

Becky Klein

Lead Author

Darrell Henze

Merck Research Laboratories

Lead Author

Wentao Zhu

Lead Author

Daniel Raftery

PhD

Lead Author

Topics

  • Models: Musculoskeletal