New Fronts in the Pain Wars

 In 2023, nearly 1 in 4 US adults were living with chronic pain, and 8.5% experienced pain severe enough to limit daily life or work activities. This is up from 20% and 6.9% in 2020, respectively, and reflects a broader upward trend over the past two decades.

Chronic pain — defined as pain that persists or recurs for more than 3 months — also exacts an enormous economic toll. Analyses of commercial claims data from over a million patients with chronic pain show an average annual cost of nearly $24,000 per patient. Nationally, the economic burden of managing patients with chronic pain totals more than $725 billion each year, without factoring in additional costs associated with missed work time and lost productivity.

Indeed, chronic pain is “the leading cause of years lost to disability worldwide, by a large margin,” Steven P. Cohen, MD, president-elect of the American Society of Regional Anesthesia and Pain Medicine, told Medscape Medical News.

With more Americans living in pain than ever before and the condition increasingly linked to aging, chronic illness, and social stressors, Cohen and other experts are rethinking how chronic pain is managed.

Research and clinical practice should move beyond traditional models, they argued, to approaches that are more effective, sustainable, and multidisciplinary and aim not only to reduce pain but also to restore function and improve the quality of life.

What Drives Pain?

There are three broad categories of pain: Nociceptive pain, which results from tissue damage like cuts, burns, or sprains; neuropathic pain, caused by damage to the somatosensory nervous system, as seen in conditions like diabetic neuropathy and trigeminal neuralgia; and nociplastic pain, which involves abnormal pain signal processing without clear tissue damage and includes conditions like fibromyalgia, migraine, and phantom limb pain.

David Clarke, MD, president of the Association for Treatment of Neuroplastic Symptoms and assistant director of the Center for Ethics at Oregon Health & Science University in Portland, Oregon, prefers the term neuroplastic over nociplastic. Unlike pain stemming from structural damage, neuroplastic pain is generated by changes in brain circuitry and often linked to stress, trauma, or unprocessed emotions, he told Medscape Medical News.

“Patients know ‘plastic’ means the capacity for change, so ‘neuroplastic’ better conveys that there’s hope for treatment,” he said. “This offers an explanation, based on neuroanatomy, showing what happens when the brain shifts to a neuroplastic state.”

A major factor driving the rise in chronic pain is the growing prevalence of chronic conditions such as diabetes and obesity, which have painful downstream effects, including diabetic neuropathy and orthopedic pain due to excessive weight on the hips, knees, and spine, Cohen said. Another driver is the frequency of chronic pain among cancer survivors, 20%-50% of whom experience chronic pain from either the cancer itself or secondary to surgical or treatment side effects.

The aging population is another major contributor to rising rates of chronic pain, noted Cohen, who is professor of anesthesiology, neurology, physical medicine and rehabilitation, psychiatry, and neurological surgery at Northwestern University Feinberg School of Medicine, Chicago. In fact, chronic pain has been called a “silent epidemic” in older adults.

David Copenhaver, MD, MPH, told Medscape Medical News that increasing employment demands may be driving stress that also contributes to chronic pain.

“The US has been called a ‘no-vacation nation’ because our work hours have been increasing, without sufficient time for relaxation,” said Copenhaver, chief of pain medicine and professor in the Departments of Anesthesiology and Pain Medicine and Neurological Surgery at the University of California, Davis. The United States is the only advanced economy that does not guarantee its workers paid vacation.

“For a long time, we understood the sensory component of pain, but we now know there’s a cognitive component too,” Cohen added.

The interrelationship between depression and chronic pain is well established. A 2025 meta-analysis of 376 studies showed that about 40% of participants had depression and 40% had anxiety. Patients treated for chronic pain should be routinely screened for mental health conditions, the authors recommended.

Treating Chronic Pain

For decades, the mainstay of chronic pain management relied heavily on pharmacologic treatments. Nonsteroidal anti-inflammatory drugs, antidepressants, anticonvulsants, and — in more severe cases — opioids.

While these medications can provide relief, they often come with significant side effects, limited long-term efficacy, and, in the case of opioids, a risk for opioid use disorder, overdose, and death. As awareness of these limitations has grown, so has the push toward safer, more sustainable alternatives.

Recent clinical guidelines increasingly emphasize nonpharmacologic approaches as first-line treatments for chronic pain.

The Centers for Disease Control and Prevention recommends nonpharmacologic and nonopioid therapies as the preferred management strategies for chronic pain, citing their favorable benefit-risk profiles.

Similarly, the American College of Physicians advises starting with interventions such as physical therapy, exercise, cognitive-behavioral therapy (CBT), and mindfulness for conditions like low back pain.

The American College of Rheumatology also prioritizes lifestyle and mind-body therapies over medications for osteoarthritis and fibromyalgia, underscoring a growing consensus around multidisciplinary, integrative care.

These guidelines reflect a growing recognition that chronic pain is not solely a physical condition — it also involves deeply rooted emotional and cognitive components. As a result, there is a new emphasis on psychological interventions as core elements of chronic pain management.

Psychological Interventions

Psychological interventions including CBT, mindfulness-based approaches, and hypnotherapy are showing promise not only in improving coping and function but also in altering pain processing in the brain itself.

CBT is one of the most established techniques and works by helping patients reframe maladaptive thoughts and behaviors through cognitive restructuring and reappraisal. It addresses not only the emotional and behavioral responses to pain but also the lifestyle factors that may contribute to its persistence.

Biologically, it has been shown to increase the expression of endogenous opioid endorphins, reduce proinflammatory markers like interleukin 6, and modulate neural circuits involved in pain perception.

Other mind-body therapies also show promise. Hypnotherapy, for instance, induces a focused, altered state of consciousness that allows patients to reprocess the sensory and emotional components of pain while enhancing relaxation, coping skills, and self-efficacy.

Mindfulness-based approaches train patients to observe their pain with nonjudgmental awareness. This practice has been associated with changes in brain regions involved in pain processing, regulation of pain-related neurotransmitters, and modulation of the autonomic nervous system.

Promising Interventions

Neuroplastic recovery therapy (NRT) is a method used by Clarke and his colleagues that is rooted in the idea that some forms of chronic pain are generated within the brain itself, “analogous to phantom limb pain,” Clarke explained.

Some patients find it reassuring that their pain originates in the brain rather than in damaged physical structures, he added.

“We ask patients to shift attention to the brain and away from the body part that hurts,” he explained, “and [to] think about what life stressors from the present or past — including early childhood adverse experiences — might be responsible for those symptoms.” Next steps involve digging deeper into past traumas and screening for other contributing factors like depression, anxiety, or posttraumatic stress.

Some research has shown NRT to be superior to other approaches in providing relief from chronic pain. One study compared 12 weeks of NRT with either mindfulness-based stress reduction techniques or usual care. At 26 weeks, 63.6% of the NRT arm reported being pain-free vs 25.0% and 16.7% of mindfulness-based stress reduction technique and usual care groups, respectively.

Another study compared neuroplastic-oriented therapy known as emotional awareness and expression therapy (EAET) with CBT in older veterans with chronic pain. Overall, 63% of those in the EAET group had clinically significant posttreatment pain reduction vs just 17% of those in the CBT group.

While psychological therapies are a key piece of the puzzle, experts emphasize that no single intervention is sufficient for every patient. Chronic pain is a multifaceted condition that often requires a tailored, multidisciplinary approach.

Daniel Clauw, MD, professor of anesthesiology, medicine (rheumatology), and psychiatry at the University of Michigan, Ann Arbor, Michigan, advocates for treatment plans that integrate patient education, lifestyle modifications, psychological support, management of comorbidities, and both nonpharmacologic and pharmacologic therapies.

Beyond psychosocial interventions, nonpharmacologic modalities such as physical exercise, improved sleep hygiene, chiropractic care, yoga, and tai chi also play a significant role.

These approaches aren’t just adjunctive, Clauw said, they’re supported by evidence demonstrating their ability to modulate nociceptive signaling, enhance descending pain inhibition, influence mood and emotional processing, promote neuroplasticity, and reduce central sensitization.

As interest in nonpharmacologic therapies continues to expand, neuromodulation has emerged as a distinct and rapidly advancing area within pain medicine. This approach encompasses noninvasive, minimally invasive, and surgical electrical therapies that aim to modify neural activity and alleviate pain.

New Horizons

In a recent review of chronic pain interventions, Cohen examined a range of neuromodulation techniques and emphasized the need for further research to determine their short- and long-term effectiveness, potential to reduce healthcare utilization, and the characteristics of patients most likely to benefit.

While device-based therapies aim to alter how pain signals are transmitted, researchers are also looking further upstream into the biology of pain itself for new therapeutic targets and the development of potential pharmacologic agents.

One particularly intriguing line of investigation in people with congenital insensitivity to pain may hold clues to unlocking novel, highly specific pain treatments, said Copenhaver.

Studying these individuals is exciting “because it helps uncover new molecular targets, particularly sodium channels, which sit on top of or within nerves that conduct pain signals.”

Copenhaver’s lab is investigating agents that block pain-specific sodium channels. One of them is a toxin derived from South American tarantulas, with a high selectivity for human voltage-gated sodium channel 1.7.

Other labs are pursuing similar targets, Copenhaver noted. One such example is suzetrigine, a selective inhibitor of a voltage-gated sodium channel called Na 1.8 expressed primarily in peripheral pain-sensing neurons and absent from the central nervous system, which may reduce its potential for addiction.

This first-in-class drug was approved by the US Food and Drug Administration (FDA) in January 2025 for the treatment of moderate to severe acute pain in adults.

“Suzetrigine is the first new pain medication to receive FDA approval in 25 years,” Cohen said. However, its arrival should be “greeted with cautious optimism” because pivotal studies may contain methodological flaws, including the choice of surgery (bunionectomy and abdominoplasty) and the restriction of timepoints to the first 48 hours post-surgery, he noted.

“These factors limit how much the findings can be generalized to more common and invasive surgeries, where postoperative pain persists longer,” Cohen said.

Suzetrigine is not currently approved for chronic pain, and its potential role in this setting remains unclear. In a study of suzetrigine for painful lumbosacral radiculopathy, the drug was not superior to placebo, but it does have “potential opioid-sparing properties and might be used together with opioids to reduce reliance on opioids,” he added.

Copenhaver is a recent speaker for Vertex Pharmaceuticals, Inc. Cohen is anticipated to take on a consultant role with Vertex Pharmaceuticals, Inc. Clauw reported consulting for Aptinyx, Daiichi Sankyo, Intec, Lundbeck, Pfizer, Regeneron, Samumed, Teva, Theravance, Tonix, Virios, and Zynerba and receiving research funding from Aptinyx, Cerephex, and Pfizer. He reported being involved in litigation testifying against opioid manufacturers in the states of Oklahoma and Florida. Clarke declared having no relevant financial relationships; donating book royalties, speaking fees, consulting fees, and faculty salaries to the nonprofit organization (Association for Treatment of Neuroplastic Symptoms); and receiving no salary for his presidency at the organization.

https://www.medscape.com/viewarticle/nation-pain-can-new-approaches-turn-tide-2025a1000b22