Enhance Pain Management

More than 25 million Americans suffer from daily chronic pain. New treatment options for pain are needed to reduce the number of people exposed to the risks of opioids. Through the HEAL (Helping to End Addiction Long-term) Initiative, NIH will support research to understand how chronic pain develops, making patients susceptible to risks associated with opioid use. HEAL will also develop a data sharing collaborative, new biomarkers for pain, and a clinical trials network for testing new pain therapies.

Understanding Biological Underpinnings of Chronic Pain

Virtually all individuals experience occasional episodes of acute pain. In some instances, acute pain gives rise to a chronic pain state, accompanied by changes throughout the nervous system. It is not known why certain patients develop chronic pain. Understanding the biologicial mechanisms underlying the transition from acute to chronic pain is necessary to advance pain management.


  • Collect data through the Acute to Chronic Pain Signatures Program from patients who have acute pain associated with a surgical procedure and patients who suffered from an acute musculoskeletal trauma. Form a comprehensive data set to help predict which patients will recover and which patients will develop long-lasting chronic pain.

Accelerate the Discovery and Pre-Clinical Development of Non-Addictive Treatments for Pain

Develop new, effective, and non-addictive medications and device for the treatment of pain.


  • Support discovery projects to reveal new biological targets for small molecules, biologics, natural products, and devices for the treatment of pain.
  • Engineer preclinical testing platforms to identify and profile non-addictive drugs for pain and addiction.
    • Use models that more closely mimic a variety of human pain conditions to test potential non-addictive treatments (small molecules, biologics, natural products, or devices) for acute and chronic pain.
    • Engineer human cell-based screening platforms that more closely approximate human physiology of pain and addiction to identify pharmacological probes or leads for testing new drugs and accelerate studies of new small molecule and biologic drug candidates for testing in humans.

Advance New Non-Addictive Treatments for Pain through the Clinical Pipeline

Initiate research efforts in collaboration with biopharmaceutical groups to incentivize and accelerate the development of new non-addictive pain medications.


  • Work with biopharmaceutical companies, the U.S. Food and Drug Administration (FDA), and the Foundation for the NIH (FNIH) to collect and evaluate therapeutic candidates and data contributed by academia, and biopharmaceutical and device companies for their potential as non-addictive treatment of pain and addiction. This includes new medications that were deprioritized for reasons other than safety that could be redeveloped or repurposed.
  • Collaborate with the private-sector to develop a program for sharing relevant clinical, preclinical, and pharmacokinetic data to expand knowledge about the reasons for success or failure of past pain therapy development programs.
  • Support biomarker discovery and rigorous validation to accelerate high-quality neurotherapeutic and pain clinical research toward Phase II trials.
  • Create a clinical trial network to focus primarily on Phase II trials with assets from companies through partnerships, or from academia and other sources. The network will include a clinical coordinating center, a data coordinating center, and hubs identified as “centers of excellence” able to recruit participants with specific pain conditions.
    • Through a multi-site network that can accommodate new trial designs, validate specific biomarkers in patients with specific well-characterized pain conditions with a high unmet medical need.
    • Promote effective training and process consistency among clinical trial sites, and streamline selection and approval of protocols.
    • Reduce start-up times, incentivize testing, and de-risk the challenges of Phase II clinical trials to accelerate the approval of effective, non-addictive therapies for treating pain.

This page last reviewed on June 12, 2018