The Economic burden of opioid-related serious adverse events and undertreatment of acute pain in the United States.

Acute pain has become increasingly prevalent in the United States due to an aging population, rising metabolic disease rates, and growth in surgical procedures. Opioids remain the primary treatment for moderate-to-severe acute pain but are associated with serious adverse events, including misuse, dependency, opioid use disorder, and overdose. In contrast, restrictive prescribing may result in undertreatment of acute pain and progression to chronic pain ("chronification"), generating additional long-term costs. As an accompanying analysis to our prior work on the increasing burden of acute pain in the wake of the opioid crisis, this study estimates the annual U.S. economic burden attributable to opioid-related serious adverse events and undertreatment of acute pain, including chronification. An economic analysis was performed to estimate direct healthcare costs and indirect productivity losses, with all values adjusted to 2024 U.S. dollars. The total annual economic burden was estimated at $425.0 billion (range: $164.5-$1,215.5 billion). Direct costs were driven by dependency, misuse/abuse, OUD, and chronic pain, while productivity losses were dominated by fatal overdoses and chronification. These findings highlight the substantial economic consequences of both opioid-related harms and inadequate pain management, demonstrating the urgent need for pain management strategies that adequately treat acute pain while minimizing the risk of serious adverse events.