A Holistic Approach to Study Non-Addictive Natural Products for Pain Management

The National Center for Complementary and Integrative Health (NCCIH) intends to publish a Notice of Funding Opportunity (NOFO) to support collaborative interdisciplinary research that advances foundational understanding of non-addictive natural products for chronic pain management through a holistic, system-oriented approach. This initiative aligns with the NIH Helping to End Addiction Long-term (HEAL) Initiative by promoting safe, non-addictive, and prevention-oriented strategies for pain relief. Chronic pain affects tens of millions of adults in the United States, contributing to disability, diminished quality of life, and significant healthcare costs. Despite widespread public use of natural products, such as botanicals, dietary supplements, and other naturally derived compounds for pain relief, scientific evidence has not kept pace with demand. Existing research often focuses on single molecular targets or isolated pathways, which fail to capture the complex, multisystem actions of these products. The scope of natural products under this NOFO includes those commonly used by the public as well as those with emerging usage or therapeutic potential.  Research is expected to take a holistic approach that examines how these products influence pain through coordinated biological pathways across the multiple organ systems, such as digestive, immune, vascular, musculoskeletal, lymphatic, metabolic/adipose tissues, and nervous system.  Studies should also explore dose optimization based on the principle of hormesis, where low doses may elicit beneficial or adaptive effects while higher doses could be ineffective or harmful. In addition, investigators are encouraged to identify optimal intervention timing that aligns with the dynamic phases of pain and inflammation, thereby maximizing therapeutic outcomes and supporting physiological recovery. This program emphasizes rigorous mechanistic studies that generate foundational insights to inform future translational research and guide the development of safe, evidence-based, non-addictive strategies for pain management.