SBIR-STTR Award

We propose to identify biomarkers associated with pain and design a biomarker assay that can be used by scientists to study pain in many different diseases/conditions. Two biomarker discovery strategies will be used to identify candidate biomarkers in diseases associated with chronic pain. Diseases include fibromyalgia, rheumatoid arthritis and osteoarthritis. From a literature search, we have identified over 180 candidate biomarkers associated with pain. To verify each molecule using antibodies would be costly. Hence, we propose mass spectrometry based approaches that can identify hundreds of proteins from small sample sets. The first biomarker discovery strategy is the proteomic analysis of protein complexes isolated from plasma. We have been successful at identifying different protein sets from different diseases using this approach and think this is a feasible approach for this study. The second strategy is the proteomic analysis of small proteins isolated from plasma. We expect to find small neuropeptides known to be associated with pain using this approach. The proteomic data will be mined to look for biomarkers and protein modification. A biomarker database will be used to select the best candidates for pain and a high-throughput assay will be designed for biomarker verification/validation.

Keywords:
Biomarker, Biomarker Discovery, Proteomics, Pain, Fibromyalgia, Rheumatoid Arthritis, Osteoarthritis, Bioinformatics

According to the Institute of Medicine of the National Academies, chronic pain affects 100 million Americans and costs the nation up to $635 billion annually. The overall objective of this project is to develop an assay to rapidly and reliably detect biomarkers associated with pain. Our goals in Phase II research are to verify the candidate pain biomarkers identified in Phase I, further develop the method, validate the biomarkers, and deliver a prototype test for pain. Mass spectrometry will be performed using direct infusion of the samples into a Thermo Scientific Q Exactive programmed to analyze 8 candidate peptide biomarkers. The use of SPE cartridges for peptide separations will be tested to determine whether test results are improved and use of lower resolution instrumentation is permitted. Peptide arrays will be used to determine whether autoantibodies are developed as part of the pain response. Validation will be performed through collaborations and/or a prospective sample collection. We expect to develop a research-grade mass spectrometry-based assay for use by scientists studying pain and diseases associated with pain.

Keywords:
Biomarkers, Mass Spectrometry, Proteomics, Diagnostic Test, Research Assay, Chronic Pain