The National Institutes of Health has launched the Acute to Chronic Pain Signatures (A2CPS) program to investigate the biological characteristics underlying the transition from acute to chronic pain. The effort will also seek to determine the mechanisms that make some people susceptible and others resilient to the development of chronic pain. A2CPS is part of the NIH-wide HEAL (Helping to End Addiction Long-term) Initiative, an aggressive, trans-NIH effort to speed scientific solutions to stem the national opioid public health crisis. The high prevalence of chronic pain in the United States, and the reliance on opioids for its management, has created an urgent need for safer, more effective pain control. Though A2CPS is part of the HEAL Initiative, its anticipated $40.4 million four-year budget is supplied by the NIH Common Fund, and is an additional investment to enhance research on pain and opioid addiction beyond funds already allocated to HEAL.