Evidence-Based Regenerative Pain Medicine with Guilherme Ferreira Dos Santos, MD CIPS

Dr. David Rosenblum sits down with Nora Rabah Rodden, founder and CEO of Nervana, a digital health app for people living with chronic pain and other persistent symptoms. During her senior year at Cornell, Nora was hit by a car, which led to five years of mid and low back pain. She tried radiofrequency ablation, PRP, steroid injections, chiropractic care, physical therapy and acupuncture, and none of them gave her lasting relief. While earning her MBA and MS in Biotechnology at Harvard, Nora enrolled as a participant in a clinical study of Psychophysiologic Symptom Relief Therapy (PSRT), led by Dr. Michael Donnino. The study combined pain education, graded exposure and journaling. Within weeks her pain dropped from a 7/10 to zero, and her insomnia and digestive problems improved too. Topics covered: How Nora went from a skeptical pain patient to building an app around the biopsychosocial model How Nervana works: pain neuroscience education, a voice-to-voice AI coach, journaling, meditation and somatic exercises. The app does not diagnose or prescribe. Why the app is "meant to be deleted," and how patients can export a one-page summary for their clinician The gap between how much the biopsychosocial model is emphasized in medical school and on the pain boards, and how hard it is to apply in a busy interventional practice A clinical story: a patient who asked for an injection for abdominal pain one month after losing her baby Why a diagnostic block is only a snapshot, and how life stressors can change pain scores How to bring up the emotional side of pain without making patients feel dismissed Why a pain physician should never tell a patient "there's nothing I can do for you" Bottom line: chronic pain is real, but the brain can turn the volume up or down. Understanding the biopsychosocial model helps clinicians offer patients more than procedures alone, and never leave them feeling there is nothing more that can be done. Guest resources: Nervana, https://www.trynervana.com. Clinicians can get free access at https://www.trynervana.com/for-clinicians For Physicians & APPs - Continue Your Education:

It's the day before the pain boards, so Dr. David Rosenblum skipped the Zoom and recorded a rapid-fire, last-minute review of the high-yield keywords and "board traps" most likely to show up on the ABA Pain Medicine exam. Listen on your commute or at the gym. High-yield topics covered Neonatal pain: A-delta and C fibers and ascending pathways work before birth, but descending inhibition is immature, so neonatal pain may be exaggerated or prolonged. Board trap: incomplete myelination does not mean neonates can't feel pain. Dorsal horn anatomy: Rexed laminae I, II and V. Lamina II is the substantia gelatinosa. Peripheral vs. central sensitization: the "inflammatory soup" (prostaglandins, bradykinin, H+, ATP, histamine, serotonin, cytokines, NGF) causes primary hyperalgesia. NMDA activation, wind-up and expanded receptive fields cause secondary hyperalgesia and allodynia. Superficial cervical plexus (C2–C4): lesser occipital, great auricular, transverse cervical and supraclavicular nerves. Blocked behind the SCM, and useful for clavicle pain. Eagle syndrome: an elongated styloid process irritating the glossopharyngeal nerve. Pain scales: NIPS, CRIES, FLACC and modified FLACC, Wong-Baker FACES, FPS-R, NRS, VAS and PROMIS-10 Global Health. Statistics: sensitivity and specificity don't depend on prevalence, but PPV and NPV do. Type I error is a false positive (α = 0.05) and Type II error is a false negative. Acetaminophen toxicity: use the Rumack-Matthew nomogram at 4 hours or later (acute single ingestion only). N-acetylcysteine is the antidote. Buprenorphine: a high-affinity partial mu agonist and kappa antagonist, with a ceiling effect on respiratory depression. Drug toxicities: carbamazepine (SIADH, SJS with HLA-B*1502, CYP3A4 induction), methotrexate (leucovorin rescue), hydroxychloroquine (retina), TNF-α inhibitors (TB reactivation), JAK inhibitors (boxed warning for MACE, thrombosis, malignancy), NSAIDs, SSRIs/SNRIs and tramadol (hyponatremia). Muscle relaxants: baclofen, tizanidine, cyclobenzaprine, methocarbamol, metaxalone, carisoprodol (meprobamate), chlorzoxazone, dantrolene, diazepam and botulinum toxin (cleaves SNARE proteins). Upcoming events Coming up: the NY/NJ Pain Congress in November and the Latin American Pain Society meeting next year. Hands-on NRAP ultrasound courses in New York are coming up in October and November. See the calendar at nrappain.org. Taking the boards next year? Start here:

Artificial intelligence is moving fast from buzzword to clinical tool — and pain medicine is no exception. In this episode, Dr. David Rosenblum breaks down how AI is already touching the field, drawing on "Artificial Intelligence and Pain Medicine: An Introduction" by Hagedorn, George, Aiyer, Schmidt, Halamka, and D'Souza (Journal of Pain Research, 2024;17:509–518). Topics covered: Why AI is expected to be a genuine turning point for healthcare, not just another tech trend Using machine learning to optimize clinical trial design and patient selection in pain research Natural language processing (NLP) tools that streamline physician workflow and improve doctor-patient communication Deep learning approaches to analyzing patient outcomes and predicting who responds best to a given treatment What better disease recognition and treatment selection could look like in day-to-day pain practice Practical implications for cost and time savings, product development, and clinical decision-making Where the evidence is still early, and what physicians should watch for as AI tools move toward the bedside Bottom line: AI won't replace clinical judgment in pain medicine, but it's already starting to augment it — from trial design to the exam room. Physicians who understand where the technology is headed will be best positioned to use it well. Reference: Hagedorn JM, George TK, Aiyer R, Schmidt K, Halamka J, D'Souza RS. Artificial Intelligence and Pain Medicine: An Introduction. J Pain Res. 2024;17:509–518. https://pmc.ncbi.nlm.nih.gov/articles/PMC10848920/

Ketamine clinics have exploded worldwide, offering low-dose intravenous infusions for chronic pain patients who've run out of options. But is this practice actually backed by evidence, or has off-label use outpaced the science? In this episode, Dr. David Rosenblum reviews the current literature on subanaesthetic-dose ketamine infusions (SDKIs) for chronic pain, drawing on the 2023 British Journal of Pain review by Harry M. Griffiths, "Low-dose ketamine infusions for chronic pain management: Does this qualify as evidence-based practice?" Topics covered: Why conventional analgesics (opioids, anticonvulsants, antidepressants) fail in 60-70% of chronic pain patients - How ketamine works as an NMDA receptor antagonist, and why that mechanism is likely an oversimplification - Typical SDKI dosing (~0.35-0.5 mg/kg) versus anesthetic dosing, and why the IV route dominates the evidence base - What the meta-analyses actually show: modest, time-limited pain reduction with higher efficacy but more side effects at higher doses - Key trials, including Corriger et al.'s 1-year follow-up (256 patients) and Orhurhu et al.'s systematic review and meta-analysis - Common side effects (nausea, psychomimetic symptoms) versus rare but serious adverse events, and how premedication with clonidine/midazolam affects risk - Why blinding failure may be inflating reported effect sizes - The absence of standardized protocols, guidelines, or a clear "exit strategy" for long-term SDKI therapy Bottom line: SDKIs offer a promising but still under-evidenced option for refractory chronic pain, reserved for the right patient with modest expectations and careful monitoring.

PainExam Podcast Show Notes NAD+ Supplementation in Pain and Inflammation: Hype, Hope, or Emerging Science? Hosted by: PainExam Podcast Presented by: NRAP Academy (Neuromodulation, Regional Anesthesia & Pain) Host: David Rosenblum, MD Episode Overview In this episode of the PainExam Podcast, we explore the growing interest in NAD+ (Nicotinamide Adenine Dinucleotide) supplementation and its potential role in pain management, inflammation reduction, cellular recovery, and healthy aging. NAD+ is a naturally occurring coenzyme found in every living cell and is essential for energy production, mitochondrial function, DNA repair, and cellular resilience. As NAD+ levels decline with age, chronic stress, inflammation, and disease, researchers have begun investigating whether restoring NAD+ levels may improve outcomes in chronic pain conditions and inflammatory disorders. We review the current science, discuss potential mechanisms of action, and examine how NAD+ therapy is being integrated into regenerative medicine, wellness programs, and pain management practices. What is NAD+? NAD+ is a coenzyme involved in: ✅ Cellular energy production (ATP generation) ✅ Mitochondrial health ✅ DNA repair pathways ✅ Oxidative stress reduction ✅ Neuroprotection ✅ Cellular signaling ✅ Activation of longevity-associated proteins called sirtuins Without adequate NAD+, cells become less efficient at producing energy and managing inflammation. Why Might NAD+ Matter in Chronic Pain? Many chronic pain conditions involve: Mitochondrial dysfunction Oxidative stress Neuroinflammation Peripheral and central sensitization Impaired cellular recovery Researchers hypothesize that optimizing NAD+ levels may help address several of these pathways simultaneously. Potential areas of interest include: Neuropathic Pain NAD+ may support: Nerve repair Axonal recovery Mitochondrial function within neurons Reduction of oxidative injury Inflammatory Pain NAD+ influences inflammatory signaling pathways and may help modulate: Cytokine production Immune cell activity Cellular stress responses Fatigue and Recovery Patients with chronic pain frequently report: Fatigue Brain fog Reduced exercise tolerance Poor recovery Because NAD+ plays a critical role in energy metabolism, some clinicians report improvements in energy and recovery following supplementation. Potential Mechanisms of Action 1. Improved Mitochondrial Function Mitochondria generate ATP, the body's energy currency. Reduced NAD+ levels are associated with: Cellular aging Impaired energy production Increased inflammation Supplementation may help restore mitochondrial efficiency. 2. Activation of Sirtuins Sirtuins are proteins involved in: Cellular repair Longevity Metabolic regulation Inflammation control NAD+ serves as a critical substrate for sirtuin activity. 3. DNA Repair Support NAD+ is required for enzymes known as PARPs (Poly ADP Ribose Polymerases), which participate in DNA repair processes following cellular injury. 4. Reduction of Oxidative Stress Chronic inflammation often produces excessive reactive oxygen species (ROS). NAD+ may help maintain cellular antioxidant defenses and reduce oxidative injury. Routes of NAD+ Supplementation Intravenous (IV) NAD+ Most commonly marketed in wellness and recovery clinics. Potential advantages: Direct systemic delivery Avoids gastrointestinal absorption issues Allows higher dosing protocols Potential limitations: Cost Time commitment Variable evidence base Oral Precursors Rather than NAD+ itself, many supplements provide precursors such as: Nicotinamide Riboside (NR) Nicotinamide Mononucleotide (NMN) These compounds are converted into NAD+ within the body. What Does the Evidence Show? Current evidence remains preliminary. While preclinical and mechanistic studies are promising, large-scale randomized controlled trials evaluating NAD+ specifically for chronic pain are still limited. Areas u