The widespread use of opioids to treat acute and chronic pain contributed to the approximately 10.3 million people aged 12 years and older in the United States in 2018 who misused opioids. These staggering numbers are likely underestimates as they fail to capture the full extent of the damage of the opioid crisis. The NIH launched the Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®, to provide scientific solutions to the opioid crisis and offer new hope for individuals, families, and communities affected by this devastating crisis. As part of the HEAL Initiative®, the NIH established the Early Phase Pain Investigation Clinical Network (EPPIC-Net), which serves to advance phase 2 clinical trials that target pain conditions of unmet need.