In recent years, pain management has remained largely unchanged despite significant advances in other areas of medicine such as oncology and cardiology. While fields like cancer treatment have embraced new therapies, the main options for pain relief continue to rely on old drugs, including opioids whose basic mechanism dates back thousands of years.
This situation presents two intertwined public health challenges. Opioids remain the most effective option for moderate to severe pain but are linked to a crisis of addiction and overdose deaths. In 2023, nearly 80,000 Americans died from opioid-related drug overdoses. Most people who died had initially been exposed to opioids through legitimate prescriptions for pain before turning to illicit drugs like heroin or fentanyl. "Even short-term use of opioids for acute pain during post-surgical recovery carries addiction potential. In 2023, nearly 80,000 Americans died of drug overdoses involving opioids, and most were patients first exposed to the drugs via legitimate prescriptions for pain," according to executives at Tris Pharma.
The widespread risks associated with opioids have led many healthcare professionals and patients to avoid their use altogether, leaving some acute pain undertreated. In the United States, only about 15%–20% of acute pain cases are now treated with opioid prescriptions.
Pain management is considered behind other therapeutic areas when it comes to innovation. Drugs like aspirin, lidocaine, acetaminophen and ibuprofen have been in use for decades or longer. Opioid-based medications such as morphine and oxycodone have dominated severe pain treatment for more than a century but come with substantial risk.
Doctors are increasingly hesitant to prescribe opioids due to fears over lawsuits, regulatory scrutiny and negative outcomes related to addiction and overdose statistics. Patients also refuse these medications more often because of personal experience or media coverage highlighting the dangers.
Research indicates that undertreated acute pain can lead to chronic conditions due to changes in nerve function after an injury heals. As of 2021, chronic pain affected more than 51 million adults in the U.S., resulting in daily life impairment for over 17 million people and economic costs exceeding $600 billion annually.
Developing new non-addictive treatments has proven difficult because pain involves complex pathways without clear biomarkers for drug development. A Biotechnology Industry Organization (BIO) study in 2023 found that only about 0.7% of new pain drugs reached FDA approval—one of the lowest rates across all therapeutic categories.
As a result, pharmaceutical companies scaled back investments in this area during the past decade. Major firms closed their research divisions focused on pain due to high risks and low returns; venture capital also shifted away from this field.
However, there are signs that change is underway. Some companies are developing novel approaches targeting mechanisms such as voltage-gated sodium channels (NaV1.8), which transmit pain signals but do not affect reward pathways associated with addiction risk. Vertex Pharmaceuticals received FDA approval in January 2025 for Journavx (suzetrigine), an oral NaV1.8 inhibitor designed for moderate-to-severe acute pain—the first major new class of non-opioid analgesic approved in decades.
Other companies are advancing similar treatments: Latigo Biotherapeutics launched with $135 million in funding and reported positive early-stage results on its NaV1.8 blocker LTG-001; SiteOne Therapeutics was acquired by Eli Lilly after progress on its own candidate STC-004.
Tris Pharma has advanced a dual NMR agonist (NOP/MOP receptor agonist) through Phase III trials as another alternative mechanism distinct from traditional opioid drugs like morphine or fentanyl.
These developments have encouraged renewed investment from both large pharmaceutical firms and venture capitalists; startups focused on non-opioid solutions have raised hundreds of millions over the past two years. The FDA has also shown support by fast-tracking non-opioid candidates amid urgent calls for alternatives.
Industry leaders emphasize that momentum must continue if real change is expected: "To dismantle the opioid paradigm, this momentum must endure," they state in their release. Regulatory incentives such as expedited reviews or guaranteed periods of market exclusivity may be necessary alongside increased federal funding dedicated specifically toward advancing safe and effective new treatments for acute pain.
With an estimated 40 million American adults experiencing acute pain treatable only by opioids each year—a number likely to grow as the population ages—the stakes remain high for developing better solutions that provide robust relief without risking addiction or overdose.
