Understanding the Brain's Role in Chronic Pain

The obsession with eliminating pain keeps patients stuck. After 15 years treating chronic pain, I've realized we're asking the wrong question entirely. Here's the shift that changed everything for my patients: 1. The "Zero-Pain" Delusion Our culture has created an impossible standard: • Perfect comfort 24/7 • Instant relief from any discomfort • Pain as a "failure" of treatment This is like demanding zero stress, zero sadness, or zero challenge in life. It's not just unrealistic—it's harmful. 2. The Real Problem When patients chase perfect relief, they: • Become hypervigilant to every sensation • Catastrophize normal body signals • Avoid movement and activities • Develop learned helplessness The research backs this up: Studies on hedonic adaptation show that our brains quickly return to baseline even after significant pain reduction. Chasing the high of "zero pain" creates a cycle of disappointment. 3. The Protocol Shift Instead of asking "How bad does it hurt?" I teach patients to ask: "How freely can you live with-and learn from-the signals your body sends?" This isn't about accepting suffering. It's about: • Normalizing pain as information, not emergency • Building confidence in your body's resilience • Focusing on function over sensation • Developing pain literacy, not pain fear 4. The Neuroplasticity Truth Here's what brain research tells us: The more attention we give to pain, the stronger those neural pathways become. But when we shift focus to movement, purpose, and gradual exposure—the brain literally rewires itself. Pain becomes background noise instead of the main event. 5. Making Pain Boring My most successful patients don't have zero pain. They have zero drama around their pain. They've learned to: • Acknowledge signals without panic • Move with confidence despite discomfort • Focus on what they can do, not what hurts • Trust their body's incredible capacity to adapt Pain becomes as boring as breathing—present but not consuming. The Bottom Line Stop trying to eliminate pain entirely. Start teaching your nervous system that pain is information, not emergency. The goal isn't a pain-free life—it's a pain-confident life.

🧠 Rethinking Motor Cortex Stimulation for Chronic Pain A new open-access paper by Lefaucheur et al. (2025, Brain Stimulation) challenges a key assumption in neuromodulation: that motor cortex stimulation relieves pain by engaging motor circuits. Instead, evidence from fMRI and neuronavigated TMS (nTMS) shows that the primary motor cortex is organized into motor effector regions separated by inter-effector, non-motor zones, areas linked to cognitive and affective control rather than movement. Implications for Pain Neuromodulation ⬇️ - rTMS analgesia likely arises from non-motor networks within the precentral gyrus - Standard motor-hotspot targeting may miss these pain-relevant circuits - nTMS motor mapping allows clinicians to deliberately identify and target inter-effector regions on an individual basis The authors highlight how nTMS can be combined with DTI, resting-state fMRI, and TMS-EEG to refine pain targets based on patient-specific connectivity, particularly thalamocortical and operculo-insular networks. 🧠 Bottom line: Motor cortex stimulation for pain isn’t about movement—it’s about modulating embedded non-motor networks. nTMS offers a practical path toward more precise, personalized rTMS targeting. 📄 Tracking non-motor regions of the motor cortex with navigated TMS for the treatment of chronic pain Lefaucheur et al., Brain Stimulation (2025) #ChronicPain #TMS #Neuromodulation

What if we could objectively measure pain in real-time using brain activity? Pain affects over 50 million Americans and remains a leading cause of disability worldwide. It is one of medicine's most subjective experiences - yet new methods are beginning to provide objective insights. Acute pain research typically relies on controlled laboratory settings where participants receive specific painful stimuli - thermal probes, pressure cuffs, or electrical shocks - while performing defined tasks. Our approach fundamentally differs by capturing real-world pain experiences as they naturally unfold: multi-day continuous monitoring of patients experiencing pain, combining neural signals with facial expressions to reveal stable pain signatures. In work led by Yuhao (Danny) Huang, a brilliant neurosurgeon and neuroscientist in the lab, we paired intracranial brain recordings in epilepsy patients to pain scores stored in electronic medical records. In this work published in Nature Communications Nature Portfolio, we decoded pain states directly from brain activity in naturalistic hospital settings. Using intracranial recordings from 12 epilepsy patients and individual-level classification models, we obtained 70% accuracy in distinguishing high vs. low pain states! High pain states showed increased theta and alpha activity in temporal/parietal regions and decreased high-frequency activity in cingulate and orbitofrontal brain areas. These patterns remained stable between pain reports and shifted predictably with pain onset or relief. We also found that facial dynamics from video recordings could also predict acute pain states with ~60% accuracy. There was a strong relationship between brain (iEEG) and video (facial dynamics) (R=.7). This isn't just academic curiosity. Objective pain measurement could transform: •Chronic pain management •Post-surgical care •Treatment for non-communicative patients •Personalized pain interventions We are moving toward a future where pain isn't just "rate your pain 1-10" but precise, objective biomarkers that guide treatment. Next: replicating this work on more patients and using deeper learning models to improve accuracy. And then to see how these features that encode naturalistic pain change as a function of wakefulness, pain medication, brain stimulation, and other potential novel forms of treatment. What applications do you see for objective pain measurement in your field? How can we expand this work? What questions do people have about this approach? Paper: https://lnkd.in/gBRyjSxC Lab: https://lnkd.in/g65jxsWQ X: https://lnkd.in/gzhZYQfY https://lnkd.in/gktDDrpt Yuhao (Danny) Huang Jay Gopal Bina Kakusa Amit Persad, Alice Li, Weichen Huang, Jeffrey Wang, Ashwin Ramayya, Josef Parvizi, Vivek Buch Stanford University Stanford University School of Medicine Wu Tsai Neurosciences Institute #Neurotechnology #PrecisionMedicine

For a long time, endometriosis has been treated like it only belongs in gynecology. But if you spend enough time around patients with chronic pain, you start to see something deeper: When pain lasts for months or years, the nervous system adapts to it. That’s why this January 2026 neuroimaging preprint caught my attention. The researchers used a multidimensional approach (including structural and diffusion MRI) and found brain-related differences in people with endometriosis — in areas and networks tied to: • pain processing and pain modulation • white-matter connectivity (how brain regions communicate) • cognitive functions that patients often describe as brain fog, slower thinking, or fatigue • emotional regulation (the part we rarely talk about, but patients live with every day) Here’s my take as a neurosurgeon: Chronic pelvic pain can become a whole-nervous-system problem. Not because it’s “in your head.” But because the brain and spinal cord are where pain is processed, amplified, or dampened. When a patient tells me: I’m exhausted I can’t focus My pain feels constant even when doctors say it shouldn’t I don’t assume exaggeration. I assume the nervous system has been forced to adapt for survival — and now it’s stuck in a sensitized state. This is why multidisciplinary care matters. Gyn care matters. Pain specialists matter. Pelvic floor therapy matters. And yes — brain-based pain mechanisms matter too. If you’ve been dismissed, minimized, or told you’re overreacting: you’re not. We’re just finally catching up to what many women have been describing for years. 🔗 Study (bioRxiv, Jan 6, 2026): https://lnkd.in/gRnnzFU8

A patient once asked me why their pain gets worse when they’re stressed even though the injury is physical. They said it as if stress and tissue are separate problems. They’re not. Your fascia responds to cortisol. Your immune system responds to perceived threat. Your nervous system modulates pain based on context. Stress isn’t making you imagine pain. It’s changing your tissue’s actual behavior. When you’re in chronic stress, your fascia stays contracted because your system thinks you need to fight or run. Your inflammatory response stays elevated because stress hormones are signaling danger. Your pain threshold drops because your nervous system is hypersensitized to any input that might signal more threat. All of that is physiologic, not psychological. This is why we can do perfect regenerative treatment, and if the patient’s stress response is dysregulated, their tissue still won’t heal. Their system is too busy protecting them to allow repair. So part of my job is helping patients understand this: Managing your nervous system isn’t optional self-care. It’s necessary biology. We CANNOT separate mind and body in healing. They aren’t separate in physiology. The vagus nerve connects brain, gut, fascia, and immune system. What affects one affects all of them. When physicians ignore that and only treat tissue, they miss half of what determines outcomes. When patients ignore that and only focus on mindset, they miss the structural problems that need intervention. You need both. They’re not two separate tracks. They’re one integrated system that either works together or fails together. That’s not holistic medicine. That’s just medicine done correctly. #nervousystem #stressphysiology #mindbodyconnection #regenerativemedicine #integrativecare #systemsmedicine #architectofmotion #drtammypenhollow #outcomesinsurance

Stop chasing tissues. Pain isn't an input from the tissues. It's a protective output from the brain when it concludes there's a threat. This output is produced by a "Neurotag"—a distributed neural network. In chronic pain, this network gets too good at its job. Through maladaptive plasticity, it becomes hypersensitive, facilitated, and imprecise. The result? "Cortical smudging." The brain's maps of the body lose their distinct boundaries. This leads to the spreading pain, poor localization, and motor deficits we see all the time in the clinic. Our job isn't to just "fix" the tissue. Our job is to retrain this overprotective system. We must provide the brain with credible evidence of safety. This is the "why" behind Pain Neuroscience Education (PNE), Graded Motor Imagery (GMI), and the DIMs/SIMs framework. I dropped a new blog post and infographic breaking down Lorimer Moseley's Neurotag model and its direct clinical application. Check it out here: https://lnkd.in/e9ZirY6W Are you targeting the Neurotag or just the tissues? Let me know your thoughts. 👇 #ModernManualTherapy #EclecticApproach #PainScience #Neurotag #PNE #PhysicalTherapy #Rehab #Physio #DPTstudent #GetBetterFaster 🧠

Bidirectional Feedback Loop: Stress > Pain > Stress > Pain There is a chemical and neurophysiological process driving persistent stress into the development of chronic pain. 🔹 Chronic pain linked to stress – Fibromyalgia and other chronic primary pain conditions are heavily influenced by psychosocial distress 🔹 Neuroinflammation plays a major role – Chronic stress activates microglia and astrocytes, leading to heightened pain sensitivity 🔹 Neuroplasticity changes – Stress alters pain-processing brain regions like the prefrontal cortex, amygdala, hippocampus, and somatosensory cortex 🔹 Mood disorders & pain are intertwined – Anxiety and depression are common in FM patients and share neuroinflammatory mechanisms 🔹 Autoimmunity involvement – FM-related IgG autoantibodies may sensitize nerve cells, worsening pain symptoms 🔹 Potential treatment targets – Investigating BDNF, NGF, IL-1, and fractalkine signaling could lead to new pain management strategies 🔹 Future directions – More research is needed to develop fast-acting therapies targeting neuroinflammation for chronic pain conditions Pain hurts, stress amplifies #Pain #MSK #PT

The “triple network” and chronic pain: in states of chronic pain, it’s so much more than a physical sensation; it’s a complete interplay of neural networks. Patients tend to have the “triple network” activated - the default mode network (DMN), the central executive network (CEN), and the salience network (SN). 1️⃣ The Default Mode Network (DMN): This network is active when the mind is at rest and not focused on the outside world. It's associated with self-referential thoughts and mind-wandering. In chronic pain states, the DMN is often overly active, leading patients to focus intensely on their pain and its implications, thus 'becoming their pain.' 2️⃣ The Central Executive Network (CEN): Involved in high-level cognitive functions, the CEN is crucial for focusing attention and problem-solving. In chronic pain, this network can become hyper-vigilant, constantly on alert for pain signals and potentially amplifying the perception of pain. 3️⃣ The Salience Network (SN): This network helps the brain detect and respond to important stimuli. It plays a role in switching between the DMN and CEN. However, in chronic pain conditions, the SN can become dysregulated, making it harder for individuals to shift their attention away from pain. 🔬 Recent research has shown that “traditional” psychedelics (not so much ketamine), such as psilocybin and LSD, promising results in “dissolving” this network interplay. They appear to disrupt the over-activity and rigid patterns of these networks, allowing for a 'reset' of sorts. By doing so, they offer a potential breakthrough in chronic pain treatment, providing relief not just physically, but also at a deeper, neural level. This evolving understanding of brain networks and the impact of psychedelics opens a new frontier in chronic pain management. It offers hope for a future where chronic pain is not just managed, but fundamentally altered, providing lasting relief and improved quality of life. #psychedelictherapy #psychedelicassistedtherapy #chronicpain #chronicpainmanagement #chronicpainrelief This image is from my keynote presentation at Wonderland in December - you can download the entire PDF here: https://lnkd.in/eHzkZZ9w

The Hidden Connection Between Emotions and Chronic Pain Why do some people hurt when their scans look normal? As a psychiatrist, I’ve seen this paradox countless times: pain that doesn’t line up with the images. It’s a reminder that our experience of pain isn’t just about anatomy. It’s about our minds, our history and our emotions. MRIs often show “abnormalities” in people with no pain at all. On the other hand, some of my patients live with severe pain while their scans look perfectly normal. That disconnect forces us to rethink how we understand pain. Research shows our state of emotional health (stress, anxiety, depression, trauma and even unprocessed grief) can amplify or even create pain. Sometimes, pain itself serves a protective role, acting as a shield against overwhelming feelings we’re not ready to face. In my work, I’ve seen patients experience real relief when we treat their mental and emotional health alongside their physical symptoms. Healing pain often means treating the whole person, not just the MRI. 🔸 3 Ways to Approach Pain Differently 🔸 ✅ Pain as a Signal, Not damage Pain may be alerting you to stress, trauma or emotions - not necessarily injury. ✅ Calm Your Nervous System Mindfulness, breathwork, and therapy help reset pain pathways. ✅ Stay Curious, Not Fearful.  Fear of pain can worsen it. Understanding pain’s mind-body link is empowering. “Pain is real. But it is a message from the unconscious mind, not a reflection of physical injury.” - John Sarno, MD This way of thinking doesn’t mean pain is “all in your head.” It means your brain and body work together. When we treat both the body and the mind, we give pain fewer places to hide. ♻️Please feel free to share this post to help spread awareness and support around mental health. You never know who might need this reminder today.♻️ 🔔Follow me for more insights and updates on mental health and wellness!🔔 #mentalhealth #motivation #pain #mindbody #psychiatry (Image Credit: Leedarrenh) (For educational and informational purposes only. Not medical advice.)