Summary: This study clearly shows that chronic back pain is often generated by the brain, not due to ongoing physical damage. Pain Reprocessing Therapy (PRT), which teaches patients to reinterpret their pain as harmless brain activity, significantly reduced or eliminated pain for most patients, with lasting effects even a year later. Brain scans confirmed that changing beliefs about pain also changed brain activity, further proving that chronic pain can be managed by retraining the brain.

APA Citation: Ashar, Y. K., Gordon, A., Schubiner, H., Uipi, C., Knight, K., Anderson, Z., … Wager, T. D. (2022). Effect of pain reprocessing therapy vs placebo and usual care for patients with chronic back pain: a randomized clinical trial. JAMA Psychiatry, 79(1), 13–23.

Summary: Phantom limb pain occurs when the brain continues to generate pain signals despite the limb being gone. This research found a strong link between brain reorganization and the intensity of phantom limb pain, clearly demonstrating the brain’s active role in creating pain sensations without any physical injury.

APA Citation: Flor, H., Elbert, T., Knecht, S., Wienbruch, C., Pantev, C., Birbaumer, N., … Taub, E. (1995). Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature, 375(6531), 482–484.

Summary: This review shows that the central nervous system, including the brain, can amplify and maintain pain through a process called central sensitization. Even when initial injuries have healed, this mechanism keeps pain ongoing and intense. This highlights that many chronic pain conditions are driven by brain activity rather than physical injuries alone.

APA Citation: Ashar, Y. K., Gordon, A., Schubiner, H., Uipi, C., Knight, K., Anderson, Z., … Wager, T. D. (2022). Effect of pain reprocessing therapy vs placebo and usual care for patients with chronic back pain: a randomized clinical trial. JAMA Psychiatry, 79(1), 13–23.

Summary: Our brains constantly predict and interpret sensory information, often creating sensations like pain based on expectation rather than actual tissue damage. This predictive processing explains how chronic pain can persist without injury, as the brain maintains an incorrect expectation of pain, reinforcing a cycle of ongoing discomfort.

APA Citation: Clark, A. (2013). Whatever next? Predictive brains, situated agents, and the future of cognitive science. Behavioral and Brain Sciences, 36(3), 181–204.

Summary: This article demonstrates how the placebo effect, powered by beliefs and expectations, can significantly alter pain experiences. The brain, through its emotional and evaluative processes, can create or reduce pain based purely on psychological appraisals, underscoring that chronic pain can be heavily influenced or generated by the brain.

APA Citation: Clark, A. (2013). Whatever next? Predictive brains, situated agents, and the future of cognitive science. Behavioral and Brain Sciences, 36(3), 181–204.

Summary: This review revealed that many people without pain have spinal abnormalities seen on MRI scans, such as disc bulges or degeneration. These findings demonstrate that such imaging results often do not cause pain, pointing to the brain’s central role in generating chronic pain independently of these structural changes.

APA Citation: Brinjikji, W., Luetmer, P. H., Comstock, B., Bresnahan, B. W., Chen, L. E., Deyo, R. A., … Jarvik, J. G. (2015). Systematic literature review of imaging features of spinal degeneration in asymptomatic populations. American Journal of Neuroradiology, 36(4), 811–816.

Summary: Central sensitization occurs when the brain and spinal cord become overly sensitive and hyper-reactive, amplifying pain signals even without ongoing tissue damage. This brain-driven process explains why some people experience chronic pain persistently and intensely. It highlights how chronic pain can be maintained and intensified solely by the nervous system, emphasizing the critical role of brain-based mechanisms in chronic pain.

APA Citation: Mayo Clinic Press. (n.d.). What is central sensitization and how does it relate to pain? Retrieved May 12, 2025, from https://mcpress.mayoclinic.org/living-well/what-is-central-sensitization-and-how-does-it-relate-to-pain/

Summary: This overview from Cleveland Clinic emphasizes that chronic pain, lasting over three months, can persist long after injuries heal or even without clear injuries. It describes central sensitization, where the nervous system becomes overly sensitive, amplifying pain sensations. This article highlights how chronic pain can be driven by brain and nervous system processes rather than physical issues alone, underscoring the brain’s critical role in pain persistence.

APA Citation: Cleveland Clinic. (n.d.). Chronic pain: What it is, symptoms, treatment & management. Retrieved May 12, 2025, from https://my.clevelandclinic.org/health/diseases/4798-chronic-pain

Summary: This study found Emotional Awareness and Expression Therapy (EAET), which focuses on addressing unresolved emotional issues, significantly reduced chronic musculoskeletal pain more effectively than Cognitive Behavioral Therapy (CBT). By directly targeting emotional processing, EAET demonstrated that chronic pain often involves emotional conflicts wired into brain pathways. Addressing these emotions can profoundly reduce pain, supporting the role of the brain and emotional health in chronic pain management.

APA Citation: Yarns, B. C., Lumley, M. A., Cassidy, J. T., Steers, W. N., Osato, S., Schubiner, H., & Sultzer, D. L. (2020). Emotional awareness and expression therapy achieves greater pain reduction than cognitive behavioral therapy in older adults with chronic musculoskeletal pain: A preliminary randomized comparison trial. Pain Medicine, 21(11), 2811–2822.

Summary: This study reveals that Emotional Awareness and Expression Therapy (EAET), targeting emotional awareness and processing, can significantly reduce symptoms and pain in fibromyalgia patients more effectively than basic education and similarly to Cognitive Behavioral Therapy (CBT). EAET specifically addresses the emotional factors underlying chronic pain, highlighting how deep emotional experiences and trauma influence the brain’s pain pathways. This demonstrates the crucial link between emotional processing, brain function, and chronic pain relief.

APA Citation: Lumley, M. A., Schubiner, H., Lockhart, N. A., Kidwell, K. M., Harte, S. E., Clauw, D. J., & Williams, D. A. (2017). Emotional awareness and expression therapy, cognitive behavioral therapy, and education for fibromyalgia: a cluster-randomized controlled trial. Pain, 158(12), 2354–2363.

Summary: This randomized controlled trial shows that Affective Self-Awareness (ASA), focusing on emotional awareness and processing, significantly reduced fibromyalgia pain and improved physical function. Nearly half of participants achieved substantial pain reduction, demonstrating that understanding and processing emotions directly impacts pain perception. This highlights the brain’s critical role in chronic pain and the power of emotionally-focused interventions.

APA Citation: Hsu, M. C., Schubiner, H., Lumley, M. A., Stracks, J. S., Clauw, D. J., & Williams, D. A. (2010). Sustained pain reduction through affective self-awareness in fibromyalgia: a randomized controlled trial. Journal of General Internal Medicine, 25(10), 1064–1070.

Summary: This review identifies central sensitization—a heightened sensitivity of the central nervous system—as a crucial factor in chronic migraine. The research explains how minor stimuli can cause severe pain, highlighting how central sensitization makes migraines persistent and severe. This underscores that effective migraine management involves addressing brain-based pain mechanisms to reduce this neurological hyperexcitability.

APA Citation: Suzuki, K., Suzuki, S., Shiina, T., Kobayashi, S., & Hirata, K. (2022). Central sensitization in migraine: A narrative review. Journal of Pain Research, 15, 2673–2682.

Summary: This review emphasizes central sensitization, the process where the brain amplifies pain signals, as a key reason why some chronic pain sufferers experience intense pain without significant tissue damage. Central sensitization varies greatly among individuals and conditions like fibromyalgia, arthritis, and chronic headaches. Targeting these central mechanisms, through tailored treatments that address brain processes directly, is crucial for effectively managing chronic pain.

APA Citation: Nijs, J., George, S. Z., Clauw, D. J., Fernández-de-Las-Peñas, C., Kosek, E., Ickmans, K., … & Curatolo, M. (2021). Central sensitisation in chronic pain conditions: latest discoveries and their potential for precision medicine. The Lancet Rheumatology, 3(5), e383–e392.

Summary: This review shows how chronic pain physically changes the brain through neuroplasticity, altering brain structure and connectivity. Pain-induced changes include increased sensitivity to pain, cortical reorganization, disrupted brain network connectivity, and reduced function in the brain’s natural pain-relieving systems. Understanding these brain changes is critical, as effective treatment must address and reverse these maladaptive brain adaptations.

APA Citation: Seifert, F., & Maihöfner, C. (2011). Functional and structural imaging of pain-induced neuroplasticity. Current Opinion in Anaesthesiology, 24(5), 515–523.

Summary: This article highlights that chronic pain is not just about physical signals from the body but involves learned emotional and motivational brain processes. Chronic pain results from the brain forming persistent, emotionally-driven memory traces of pain. This new understanding points towards therapies that target these brain-based learning and memory pathways, suggesting that chronic pain can be effectively managed by retraining the brain.

APA Citation: Mansour, A. R., Farmer, M. A., Baliki, M. N., & Apkarian, A. V. (2014). Chronic pain: the role of learning and brain plasticity. Restorative Neurology and Neuroscience, 32(1), 129–139.

Summary: This review discusses nociplastic pain, pain not caused by physical injury or nerve damage but by altered nervous system processing. It differentiates nociplastic pain from central sensitization but recognizes that both involve brain-based changes. Conditions like fibromyalgia and irritable bowel syndrome exemplify nociplastic pain, highlighting the need for treatments specifically targeting these altered brain processing mechanisms.

APA Citation: Bułdyś, K., Górnicki, T., Kałka, D., Szuster, E., Biernikiewicz, M., Markuszewski, L., & Sobieszczańska, M. (2023). What do we know about nociplastic pain? Healthcare (Basel, Switzerland), 11(12), 1794.

Summary: This article proposes that many cases of chronic back pain are psychophysiologic, meaning psychological processes can generate and sustain pain. Psychophysiologic Symptom Relief Therapy (PSRT) was developed to target these processes, helping patients understand that their pain is real but generated by the brain’s response to stress and emotional factors. Addressing these non-physical triggers offers a powerful path to lasting pain relief.

APA Citation: Thompson, G. S., Paschali, M., Howard, P. M., Yamin, J. B., Edwards, R. R., Mehta, S., & Donnino, M. W. (2024). Psychophysiologic symptom relief therapy for chronic back pain: hypothesis and trial rationale. Frontiers in Pain Research, 5, 1328495.

Summary: This systematic review shows that Pain Neuroscience Education (PNE) is highly effective for treating chronic musculoskeletal pain. By teaching patients how pain is influenced by the brain and nervous system—not just tissue damage—PNE reduces fear, improves movement, decreases pain, and empowers recovery. This education is a cornerstone for helping patients recalibrate their brain’s understanding of pain.

APA Citation: Louw, A., Zimney, K., Puentedura, E. J., & Diener, I. (2016). The efficacy of pain neuroscience education on musculoskeletal pain: A systematic review of the literature. Physiotherapy Theory and Practice, 32(5), 332–355.

Summary: This case series shows that mind-body treatments focusing on emotional and psychological factors can dramatically improve chronic back pain without clear structural causes. Patients diagnosed with Tension Myositis Syndrome (TMS) experienced significant pain reductions and quality of life improvements. This supports the view that brain-driven, psychophysiologic processes play a major role in many chronic pain cases and that treating these brain-based mechanisms can be highly effective.

APA Citation: Schechter, D., Smith, A. P., Beck, J., Roach, J., Karim, R., & Azen, S. (2007). Outcomes of a mind-body treatment program for chronic back pain with no distinct structural pathology–a case series of patients diagnosed and treated as tension myositis syndrome. Alternative Therapies in Health and Medicine, 13(5), 26–35.

Summary: This systematic review highlights the effectiveness of mind-body therapies like guided imagery, tai chi, yoga, and qigong in treating fibromyalgia—a condition of brain-generated, nociplastic pain. These therapies improve not only pain but also fatigue, sleep, and daily functioning by targeting the brain and nervous system directly. The findings strongly support using approaches that retrain the brain to calm the overactive nervous system and reduce chronic pain symptoms.

APA Citation: Steen, J. P., Kannan, V., Zaidi, A., Cramer, H., & Ng, J. Y. (2024). Mind-body therapy for treating fibromyalgia: a systematic review. Pain Medicine. Advance online publication. https://doi.org/10.1093/pm/pnae076.