The National Center for Complementary and Integrative Health (NCCIH) plans to publish a Notice of Funding Opportunity (NOFO) that will support a phased mechanistic clinical research program focusing on understudied biological mechanisms that drive joint pain. The initiative responds to priorities identified in the 2023 HEAL Whole Joint Pain Workshop and supports the broader goals of the NIH Helping to End Addiction Long-term (HEAL) Initiative and the Make America Healthy Again vision by advancing safe, non-addictive, and prevention-oriented approaches to chronic pain.

Joint pain affects nearly half of adults in the United States. Many current treatments provide incomplete or temporary relief, informed by clinical trials that focus on joint structures such as bone or cartilage in isolation, without addressing contributions from additional tissues comprising the “whole joint”. New advances in imaging, biomechanics, tissue-specific omics, electrophysiology, and digital health tools now allow for a more complete evaluation of the whole joint, including periarticular tissues such as muscle, adipose, ligaments, tendons, and fascia.

The phased projects supported by this program will first identify and validate multi-tissue mechanisms underlying joint pain, then test non-pharmacological or multimodal interventions that directly target these mechanisms. Please note that while applications can specify the length of time for each of the following study phases, the total project length cannot exceed 5 years:

Phase 1 (2 to 3 years): Projects will identify multisystem mechanisms that include signals from periarticular tissues (e.g., muscles, adipose, and connective tissues including ligaments, tendons, or fascia) and their potential interactions with articular tissues (e.g., bone, synovium, cartilage) or the peripheral nervous system that contribute to joint pain and pathophysiology. Studies may incorporate imaging, biomarker profiling, neuromuscular assessment, behavioral or environmental factors, and other multimodal approaches that meet or exceed NIH standards for rigor and reproducibility.

Phase 2 (2 to 3 years): Successful phase 1 projects will receive additional funding to test the impact that non-pharmacological and/or multimodal interventions have on the identified multi-tissue mechanisms, to define how these interventions work to correct pathophysiology, aid healing, and resolve pain in the joint. Proposed interventions may include physical therapy, mind-body approaches, biomechanical strategies, or integrated multimodal treatments.

This phased approach is intended to accelerate the development of safe, accessible, non-addictive strategies that improve function, mobility, and quality of life for people with chronic joint pain. It will generate high-quality mechanistic evidence that supports whole joint and whole person models of care and contributes to nationwide efforts to reduce chronic pain and opioid dependence using non-pharmacological interventions and multimodal therapies.

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