Transforming pain medicine: the power of collaboration, entrepreneurship, and innovation

The etiology of chronic pain can be difficult to pinpoint, and the condition often resists many treatments. Conservative approaches using non-opioid medications often offer inadequate relief, while opioids pose significant risks of dependence and sedation, achieving on average 30% reduction in pain intensity.1 Despite the risks, pain management has historically relied heavily on opioids. With 20% of US adults experiencing chronic pain in 2021, the need for innovative treatments—ones that not only alleviate pain but also address its underlying causes—has become evident.2 In fact, recent data indicate that chronic pain has become a more common diagnosis than diabetes, depression, or hypertension, all of which may be linked to its development.3–5 As the complexity of chronic pain becomes more apparent, greater collaboration across pain-related specialties becomes essential for developing holistic solutions. The complexity of chronic pain arises from a variety of factors, including both physiological and social determinants of health. As a result, contemporary approaches integrate multiple pain-related specialties (Figure 1). In fact, the 2019 “Pain Management Best Practices Interagency Task Force Report” by the US Department of Health and Human Services endorsed multimodal and multidisciplinary strategies as the most effective treatments for both acute and chronic pain.6 Such programs offer a broad range of treatments including medications, restorative therapies, invasive interventions, and care that addresses the social and psychological aspects of pain (Table 1). These programs, despite variance in content and duration, consistently show significant improvements in pain, mood, daily activities, and quality of life over time.6–8 Building on this success, integrative therapies like acupuncture have gained acceptance among both patients and clinicians, with clinical evidence increasingly supporting their use in areas such as cancer pain management.9 At their core, these therapies combine conventional medicine with holistic practices that address emotional, mental, and cultural dimensions of healing, thereby addressing both the physical and non-physical contributors to pain and ultimately enhancing patient experience and outcomes. Disciplines and innovation. Interdisciplinary approaches and complementary therapies for acute and chronic pain. A growing number of institutions are driving advances in pain management by guiding innovators from idea to commercialization by offering educational, business, and financial support. For example, the Stanford Pain Relief Innovations Lab offers the “Empowered Relief” class, which disseminates holistic pain relief techniques that has been shown to be as effective as multiple cognitive behavioral therapy sessions. Similarly, the Harvard Medical Device Innovation Initiative supports student-led ventures such as Poly6 Biotechnologies, which developed implantable devices to prevent pain from abdominal and pelvic adhesions. Healthcare innovation challenges, such as those hosted by MIT Hacking Medicine, foster creative solutions for holistic pain management by bringing together diverse professionals and providing a platform to showcase their concepts. These initiatives help entrepreneurs transition their ideas from concept to commercialization, assisting them in securing the necessary funding and partnerships. For instance, the American Academy of Pain Medicine (AAPM) hosted 175 companies from 30 states and 15 countries at innovation challenges over the past 3 years, with finalists raising millions in funding through AAPM's support. Notable successes include Lutroo, which developed AI-enhanced pain imaging technology and received SBIR and NIH HEAL Initiative funding; Wellness Wits, a digital health solution for chronic pain, which partnered with IBM and scaled its operations; Vanish Therapeutics, which advanced its novel drug delivery systems with significant SBIR and venture capital funding; and FaraMed Tech, which is pursuing clinical trials for a wearable neuromodulation solution. These success stories illustrate how such initiatives help entrepreneurs overcome the critical challenges of early-stage startups (Table 2). Referenced weblinks stratified by section. Advanced diagnostic technologies (e.g., PET, MRI, EEG) and biomarkers have enhanced our understanding of pain processes and prevention. Recent pharmaceutical innovations, such as ultrasound-triggered local anesthesia and photoswitchable analgesics, enable more targeted drug delivery. Minimally invasive procedures—such as IntraceptTM, VertiflexTM, Reactiv8, Mild®, Painteq®, SIFix®, and Minuteman®—have been developed to improve lower back pain. Neuromodulation devices have evolved beyond traditional spinal cord stimulation to stimulation of the dorsal root ganglion and peripheral nerve, with closed-loop algorithms from companies like Abbott and Saluda Health. Despite these advances, challenges remain—device and drug parameters often require patient-specific titration, and 28% of individuals with implanted stimulators report insufficient pain relief.10 Additionally, 26% of these patients undergo surgical revision, wherein 5% involve device removal.10 These challenges highlight the need to improve the effectiveness and longevity of implanted devices. External stimulation devices, such as transcranial magnetic stimulation (TMS), transcutaneous electrical nerve stimulation (TENS), percutaneous electrical nerve stimulation (PENS), vibration therapy, and magnetic field therapy offer safe and cost-effective pain management, though further research is needed to refine their use. Specific products like Actipatch®, Omron Avail, and Cefaly offer relief for a variety of conditions, including musculoskeletal pain, chronic pain, acute pain, arthritic pain, and migraines, while VibraCool combines cold and vibration to stimulate the body’s natural pain-relieving pathways. Beyond physical pain management, online platforms address psychological and social dimensions of pain. Innovations like NeuroSphere™ and telemedicine software facilitate remote patient management, while virtual reality (VR) technology has helped shift pain perception by distracting users from discomfort. Emerging VR technologies range from simple apps to immersive full-body experiences, with options like Applied VR, Sana Health, Flowly, Headspace, and Mindmaze. VR has also shown potential to increase pain tolerance by downregulating nociceptive signaling and upregulating non-painful cognitive signals.11 Companies such as Lin Health, Override, Menda Health, and Upside Health are establishing new digital care paradigms for behavioral therapy and chronic pain management. Overall, these technologies not only provide new treatment options but also target previously underexplored causes of pain, offering more comprehensive approaches. Adequate funding and robust industry support are crucial for bridging the gap between technological advances and clinical management of chronic pain. In the United States, traditional funding sources like the National Institutes of Health (NIH) tend to prioritize conventional approaches, particularly those focused on opioids. For example, in 2023, NIH funding for opioid research, misuse, and addiction reached $1.8 billion, while research on peripheral neuropathy, neck and back pain, and fibromyalgia combined received only $300 million, with no reported funding for interventional pain medicine.12 While industry plays a role, they primarily step in for commercialization once early concepts prove viable, making government support critical for the initial stages of research. Public-private partnerships, such as the Innovative Medicines Initiative in the EU, which funds projects like EUROPAIN and NGN-PET, offer a balanced approach by providing a mixture of public and private funding from ideation to commercialization, helping navigate the crucial transition between public and private investment in technology development. Institutions like the University of Pittsburgh’s Center for Innovation in Pain Care and The Cleveland Clinic’s Pain Science Technology and Research (STAR) Lab exemplify U.S.-based innovation efforts driven by such partnerships. The complexity of pain demands the development of holistic approaches to pain management. To fully address this multifaceted issue, it is essential for stakeholders from various fields to unite and devise comprehensive strategies that encompass all aspects of pain care. Programs that connect clinicians, entrepreneurs, and patient advocates are crucial for fostering the growth and translation of new technologies into clinical practice. One avenue for such collaboration could be formalized consortia dedicated to pain management innovation, with shared funding and resources aimed at bridging the gaps between clinical research, industry advancements, and patient needs. Further, comprehensive interdisciplinary training for researchers and clinicians is necessary to create informed, well-rounded diagnoses and pain management plans. Such training could be structured around immersive, cross-specialty modules, allowing participants to engage directly with perspectives from fields related to pain management (Figure 1). Regulatory agencies pave the way for these collaborative innovations through up-to-date guidelines. For example, the FDA’s recent regulations encourage the development of non-opioid analgesics for acute pain, promoting safer and more effective alternatives. By incentivizing projects aligned with these guidelines, we could attract investments into non-opioid development labs, supporting cross-disciplinary teams focused on alternative pain relief options. Through concerted efforts from diverse sectors, we can transform pain management and improve the lives of millions suffering from chronic pain. There are no financial conflicts to disclose pertaining to the current submission. Dr Justin E. Bird consults for Stryker, Icotec, BrainLab and GT Medical Technologies. Dr Justin E. Bird also receives research funding support from Artidis RCTS #:00061874: Strategic Alliance—Artidis Alliance—Umbrella Protocol: Pancreatic, hepatobiliary, soft tissue sarcoma, chondrosarcoma, chordoma, and lung cancers. Dr Chris Gilligan consults for Mainstay Medical, Saluda and Iliad Lifescience and receives stock options from Mainstay Medical consulting and stock options. Stanford University receives revenue for continuing medical education on Empowered Relief (ER) instructor certification training provided to clinicians. Dr Darnall is Chief Science Advisor at AppliedVR, and her consulting role with this company (personal fees) is unrelated to the current work. Dr Darnall receives royalties for four pain treatment books she has authored or co-authored. She is the principal investigator for two pain research awards from the Patient-Centered Research Outcomes Research Institute, one of which is investigating the effectiveness of ER. Dr Darnall is a principal investigator for two NIH grants investigating ER's efficacy. Dr Darnall serves on the Board of Directors for the American Academy of Pain Medicine, the Board of Directors for the Institute for Brain Potential, and the Medical Advisory Board for the Facial Pain Association. Dr Darnall is a scientific member of the NIH Interagency Pain Research Coordinating Committee, a former member of the Centers for Disease Control and Prevention Opioid Workgroup (2020–2021), and a current member of the Pain Advisory Group of the American Psychological Association. National Institute on Drug Abuse K24 DA053564 (Darnall). Conflicts of interest: The authors do not have any relevant conflict of interest to disclose.