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Abstract Introduction: Pain is a common and burdensome condition associated with significant health care costs and patient morbidity in the United States, yet limited pain prevalence data exists. Objectives: Provide national-level prevalence estimates of acute and chronic pain requiring management with prescription medication in the United States. Examine medication treatment patterns for the overall pain populations and a subset of patients with peripheral neuropathic pain (PNP). Methods: This study used a retrospective cross-sectional design that identified adults receiving treatment for pain in 2022 in the MarketScan Commercial and Medicare Supplemental and the Premier Healthcare Databases. Pain prevalence and medication use were analyzed and extrapolated to the United States population using standardized prevalence estimation methods. Results: Results suggest that approximately 102.1 million (M) people in the United States received prescription pain medication in 2022. Approximately 28.7M people received prescription medications for chronic pain, of which 11.1M (39%) had PNP conditions. Most patients with chronic pain used prescription nonsteroidal anti-inflammatory drugs (NSAIDs; 51%), anticonvulsants (44%), opioids (41%), and antidepressants (40%). Anticonvulsant use was more prominent in PNP (62% of patients had ≥1 prescription). Acute pain was estimated to affect 80.2M adults in the United States; 46.2M people with pain medication administered in-hospital, 43.5M filling prescription pain medications and 9.4M in both settings. Among all acute pain patients, 48% and 42% had evidence of opioid and NSAID use, respectively. Approximately 6.8M patients with chronic pain also experienced an acute pain event in-hospital. Conclusion: Findings show pain, pain medication use, and opioid-use in particular, are highly prevalent in the United States.