Off-label use and access issues

Pain is probably the oldest problem in medicine. It’s the way our bodies tell us that something is wrong here.

But pain has long been considered a symptom. So when medicine can’t find what’s wrong, or when medicine can’t fix the pain, well, that’s usually the end of the story. And that’s left a lot of people with chronic pain suffering in silence.

In this episode, we learn why pain is one of the great mysteries of medicine - one of the most challenging conditions to diagnose, to measure, and to treat successfully.

We explore why the worthy effort to bring pain into the light inadvertently created what may be the most devastating social crisis (ahem, opioid epidemic) of the last century.

And we look at a new pain medicine - Journavx - which is not approved for chronic pain (yet) but has a lot of people hoping for a path to peace without addiction.

Sources for this episode

[1]  "Wrestling With Pain:" John J. Bonica, MD. Autobiography (1987) The International Symposium on Pain Analgesia: Dr. John J. Bonica recounts his life as a "wrestling match" against medical indifference to establish the multidisciplinary approach to pain therapy. 

[2] Oral History Interview with John J. Bonica (1993) John C. Liebeskind History of Pain Collection: John Bonica is widely regarded as the founding father of pain management.

[3] International Symposium on Pain (1974) Raven Press: Proceedings from the first major international meeting on pain research and management.

[4] Individual Differences in Pain: Understanding the Mosaic that Makes Pain Personal (2017) PAIN: Explains how biological, psychological, and social factors shape personal pain experiences.

[5] Chronic Pain: What Does It Mean? A Review on the Use of the Term Chronic Pain in Clinical Practice (2021) Journal of Pain Research: "Chronic pain" is a semantically inaccurate and potentially misleading clinical label because it overemphasizes duration while failing to account for biopsychosocial factors.

[6] Prevalence of Depression and Anxiety in Chronic Pain (2025) JAMA: Systematic review and meta-analysis showing high rates of depression and anxiety among adults with chronic pain.

[7]  Improving Outcomes of Analgesic Treatment: Is Education Enough? (1990) Annals of Internal Medicine: The persistent undertreatment of pain is rooted in a historical medical focus on physical lesions over subjective symptoms. 

[8]  Pain as the 5th Vital Sign Toolkit (2000) The Veterans Health Administration: A comprehensive guide developed by the Veterans Health Administration (VHA) to institutionalize a standardized, system-wide approach to managing patient discomfort.

[9] A Capsule History of Pain Management (2003) JAMA: Historical overview of approaches to managing pain, from ancient remedies to modern treatments.

[10] Bridging Old and New in Pain Medicine: An Historical Review (2023) Cureus: Historical review linking traditional pain remedies with modern medical practices.

[11] The Opioid Epidemic: It’s Time to Place Blame Where It Belongs (2017) The Journal of the Missouri State Medical Association: Dr. Ronald Hirsch argues that the opioid crisis was driven by a network of "co-conspirators" including pharmaceutical companies, medical oversight organizations, and government agencies.

[12] The 5th Vital Sign and America’s Painkiller Epidemic (2016) The University of Arizona Health Sciences: The institutionalization of pain management led to a surge in prescription drug abuse and overdose deaths. 

[13]  The Promotion and Marketing of OxyContin: Commercial Triumph, Public Health Tragedy (2008) The American Journal of Public Health: Oxycotin’s commercial success was driven by predatory marketing tactics, such as targeting high-volume prescribers and systematically understating the risk of addiction.

[14]  The fifth vital sign: A complex story of politics and patient care (2016) Cleveland Clinic Journal of Medicine: Aggressive marketing and institutional mandates minimized the perceived risks of addiction, leading to the current opioid epidemic.

[15] The Pain and Opioid Epidemics: Policy and Vital Signs (2016) JAMA Health Forum: The historical movement to treat pain as a fifth vital sign inadvertently fueled a massive increase in narcotic prescriptions.

[16] Addiction Rare in Patients Treated with Narcotics (1980) The New England Journal of Medicine: a 1980 letter to the editor of the New England Journal of Medicine covers the low incidence of narcotic addiction in medical settings.  

[17] Remove Pain as 5th Vital Sign, AMA Urged (2016) Medpage Today: Medical professionals at an American Medical Association met to advocate for the removal of pain as a "fifth vital sign".

[18] FDA Approves Novel Non-Opioid Treatment for Moderate to Severe Acute Pain (2025) US Food & Drug Administration: FDA announcement of approval for a new, non-opioid treatment for moderate to severe acute pain.

[19] F.D.A. Approves Drug to Treat Pain Without Opioid Effects (2025) The New York Times: The FDA approved a non-opioid painkiller developed by Vertex.

[20] What Is Journavx, the New Opioid-Free Painkiller from Vertex? (2025) Scientific American: Journavx functions by blocking sodium ion channels to stop pain signals before they reach the central nervous system, offering a mechanism entirely different from traditional treatments.

[21] Painkillers without the addiction? The new wave of non-opioid pain relief (2025) Guaridian:  The pharmaceutical industry is shifting toward developing non-opioid pain relief to address the devastating global addiction crisis.

[22] An SCN9A channelopathy causes congenital inability to experience pain (2006) Nature: Discovery that mutations in the SCN9A gene cause congenital inability to experience pain.

[23] Chronic Pain Is a Hidden Epidemic. It’s Time for a Revolution. (2025) The New York Times Magazine: Opinion piece calling for a revolution in how chronic pain is addressed in society.