The purpose of this Funding Opportunity Announcement (FOA) is to promote the discovery of strong candidate biomarkers or biomarker signatures for pain that can be used to facilitate the testing of non-opioid pain therapeutics in Phase II clinical trials. The biomarkers or biomarker signature will be developed through clinical research specifically focused on the identification of pain biomarkers or biosignatures that predict and/or monitor response to pain therapeutics. The resulting biomarkers or biomarker signatures may be focused on a single pain condition or on several pain conditions with common underlying pathophysiology. Applications to identify biomarkers or biomarker signatures that predict or monitor a therapeutic response across several related pain conditions should feature Multiple Principal Investigator (MPI)-led teams that represent each of the related pain conditions and associated clinical networks. The MPI-led teams are expected to decide upon a single set of measures or biomarker modalities (i.e., combination of omics, QST, actigraphy, EEG, digital measures, etc.) as components of the biosignature for all pain conditions represented in the application. Applications should feature centralized resource groups that will coordinate clinical trials and standardize all sample or data collection methods, technology development, statistical analysis and algorithm development across the pain conditions under investigation. Applications seeking to develop biomarkers or biomarker signatures that will be used to predict and/or monitor a therapeutic response for a single pain condition must also feature MPI-led teams that represent the cross functional expertise necessary for biomarker and/or signature development, along with the same types of centralized resource groups that coordinate clinical trials and standardize sample or data collection methods, technology development and statistical analysis.