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Effect of Pain Reprocessing Therapy vs Placebo and Usual Care for Patients With Chronic Back Pain: A Randomized Clinical Trial
Open accessAbstract
Importance: Chronic back pain (CBP) is a leading cause of disability, and treatment is often ineffective. Approximately 85% of cases are primary CBP, for which peripheral etiology cannot be identified, and maintenance factors include fear, avoidance, and beliefs that pain indicates injury. Objective: To test whether a psychological treatment (pain reprocessing therapy [PRT]) aiming to shift patients' beliefs about the causes and threat value of pain provides substantial and durable pain relief from primary CBP and to investigate treatment mechanisms. Design, Setting, and Participants: This randomized clinical trial with longitudinal functional magnetic resonance imaging (fMRI) and 1-year follow-up assessment was conducted in a university research setting from November 2017 to August 2018, with 1-year follow-up completed by November 2019. Clinical and fMRI data were analyzed from January 2019 to August 2020. The study compared PRT with an open-label placebo treatment and with usual care in a community sample. Interventions: Participants randomized to PRT participated in 1 telehealth session with a physician and 8 psychological treatment sessions over 4 weeks. Treatment aimed to help patients reconceptualize their pain as due to nondangerous brain activity rather than peripheral tissue injury, using a combination of cognitive, somatic, and exposure-based techniques. Participants randomized to placebo received an open-label subcutaneous saline injection in the back; participants randomized to usual care continued their routine, ongoing care. Main Outcomes and Measures: One-week mean back pain intensity score (0 to 10) at posttreatment, pain beliefs, and fMRI measures of evoked pain and resting connectivity. Results: At baseline, 151 adults (54% female; mean [SD] age, 41.1 [15.6] years) reported mean (SD) pain of low to moderate severity (mean [SD] pain intensity, 4.10 [1.26] of 10; mean [SD] disability, 23.34 [10.12] of 100) and mean (SD) pain duration of 10.0 (8.9) years. Large group differences in pain were observed at posttreatment, with a mean (SD) pain score of 1.18 (1.24) in the PRT group, 2.84 (1.64) in the placebo group, and 3.13 (1.45) in the usual care group. Hedges g was -1.14 for PRT vs placebo and -1.74 for PRT vs usual care (P < .001). Of 151 total participants, 33 of 50 participants (66%) randomized to PRT were pain-free or nearly pain-free at posttreatment (reporting a pain intensity score of 0 or 1 of 10), compared with 10 of 51 participants (20%) randomized to placebo and 5 of 50 participants (10%) randomized to usual care. Treatment effects were maintained at 1-year follow-up, with a mean (SD) pain score of 1.51 (1.59) in the PRT group, 2.79 (1.78) in the placebo group, and 3.00 (1.77) in the usual care group. Hedges g was -0.70 for PRT vs placebo (P = .001) and -1.05 for PRT vs usual care (P < .001) at 1-year follow-up. Longitudinal fMRI showed (1) reduced responses to evoked back pain in the anterior midcingulate and the anterior prefrontal cortex for PRT vs placebo; (2) reduced responses in the anterior insula for PRT vs usual care; (3) increased resting connectivity from the anterior prefrontal cortex and the anterior insula to the primary somatosensory cortex for PRT vs both control groups; and (4) increased connectivity from the anterior midcingulate to the precuneus for PRT vs usual care. Conclusions and Relevance: Psychological treatment centered on changing patients' beliefs about the causes and threat value of pain may provide substantial and durable pain relief for people with CBP. Trial Registration: ClinicalTrials.gov Identifier: NCT03294148.
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“In a study on patients with chronic lower back pain, it produced significant pain relief relative to placebo and usual care, mediated by decreased fear and threat beliefs (Ashar et al., 2022).”
From Listen to your inner body: embodied emotions in predictive neuroscience and traditional East Asian medicine (2026) · cites this paper as Ashar et al., 2022
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“There are highly successful therapeutic approaches, notably to chronic back pain, that proceed from this insight, engage with catastrophic thinking and give it a positive twist [22].”
From Endometriosis: patient–doctor communication and psychological counselling (2023) · cites this paper as [22]
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Rani, V. I., Jha, V. K., Padma, V., Rengaramanujam, K., Mahapatra, A. P. K., & Prabha, K. S. (2026) · Physiotherapy Quarterly · doi:10.5114/pq/211756
“Perron et al. [29] and Pairot de Fontenay et al. [26] emphasised tailored programs for physically demanding roles like military personnel, demonstrating reduced injury rates [34].”
Thomson, C. J., Holden, K. N., Giles, L. V., & Cianfrini, L. R. (2026) · Canadian Journal of Pain · doi:10.1080/24740527.2026.2650304
Jurado, A. J. N. (2026) · Atención Primaria · doi:10.1016/j.aprim.2026.103513
Frisch, S., & Tesarz, J. (2026) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2026.112862
Wynia, Z., Gasienica, J., Amondson, R., Heil, J., Nolan, C., Cox, L., Truesdell, V., Frank, J. W., & Ashar, Y. K. (2026) · Journal of Pain · doi:10.1016/j.jpain.2026.106322
Self-citationVoluntary attention regulates acute immune responses in humans
Mizrachi, N., Rottem, M., & Rozenkrantz, L. (2026) · Nature Human Behaviour · doi:10.1038/s41562-026-02541-1
Boehnke, K. F., Pouyan, N., & Aday, J. S. (2026) · Drugs · doi:10.1007/s40265-026-02339-5 · Cited by 2
Coulombe-Lévêque, A., Bonin, R. P., & Léonard, G. (2026) · Pain · doi:10.1097/j.pain.0000000000004013 · Cited by 1
“…for chronic pain are mixed approaches such as the Pain Neuromatrix approach, 120 Cognitive Functional Therapy, 133 and Pain Reprocessing Therapy, 6 which target explicit beliefs (through various education modalities, notably Pain Neuroscience Education) and implicit associations (through…”
Interictal avoidance of sensory stimuli among individuals with migraine
Rogers, D. G., Protti, T. A., & Smitherman, T. A. (2026) · Headache The Journal of Head and Face Pain · doi:10.1111/head.70142
“55,56 To the extent interictal avoidance represents a manifestation of trigger beliefs or generalized fear avoidance, these processes may provide novel intervention targets for exposure-based”
Su, D.-M., Li, Z.-H., Xiong, Y., Xiong, D., Yang, D., & Zhou, J. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1851073
Proposed Conditions for Pain Reprocessing Therapy Readiness: Beyond Phenotyping Neuroplastic Pain
Thérond, A., Starnino, L., & Robinson, C. L. (2026) · Current Pain and Headache Reports · doi:10.1007/s11916-026-01518-z
“Somatic tracking, emotional processing, and cognitive reappraisal all require patients to participate rather than receive treatment passively [2].”
Christine, D., Brinkman, V., Slagboom, M. N., Vos, H. M. M., & Bussemaker, J. (2026) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2026.112820
Zetterberg, H., Zhao, X., Bergbom, S., Lennartsson, R., Flink, I. K., Linton, S. J., & Boersma, K. (2026) · European Journal of Pain · doi:10.1002/ejp.70310
“This treatment model is one of a range of new treatment approaches that aim to target pain–emotion connections explicitly and directly (Ashar et al. 2022; Lumley and Schubiner 2019; Michal et al. 2025; Norman-Nott et al. 2022).”
Reply to Noe-Steinmuller and Tesarz
Sullivan, M. D., & Williams, A. C. D. C. (2026) · Pain · doi:10.1097/j.pain.0000000000003992
Flegge, L. G., Penman, J. C., Tracy, C., & Bushey, M. A. (2026) · Global Advances in Integrative Medicine and Health · doi:10.1177/27536130261456244
Jenkins, L. C., Bilska, K., Cashin, A. G., Chang, W., Nicholas, M., McAuley, J. H., & Schabrun, S. M. (2026) · Pain · doi:10.1097/j.pain.0000000000004023
The Placebo Effect in Pain: Mechanisms, Applications, and Ethical Considerations
Sun, J., & Zhang, X. (2026) · International Journal of Pain Research · doi:10.11648/j.ijpr.20260202.15
Wu, Y., Kong, Q., Saccà, V., Reddy, S., Hodges, S., Li, Y., & Kong, J. (2026) · Brain Research · doi:10.1016/j.brainres.2026.150447
Psychosocial Interventions for Chronic Non-Cancer Pain Among Older Adults: A Scoping Review
Low, E. L., Gibson, S. L., Patel, K. B., Hickner, A., Sanni, M., Scher, C. J., & Reid, M. C. (2026) · Journal of Applied Gerontology · doi:10.1177/07334648261462221
ХРОНИЧЕСКИЙ БОЛЕВОЙ СИНДРОМ: СОВРЕМЕННЫЕ ПОДХОДЫ К ДИАГНОСТИКЕ И ЛЕЧЕНИЮ
Shibitova, D. V., Пекур, И. А., Равилевна, С. Ф., Жанакулова, Ж. М., & Акболат, Л. (2026) · International Journal of Applied and Fundamental Research (Международный журнал прикладных и фундаментальных исследований) · doi:10.17513/mjpfi.13793
Threats to social safety and pain: A global study
Baranik, L. E., Gorman, B., Seguin, C., & Schubiner, H. H. (2026) · Journal of Pain · doi:10.1016/j.jpain.2026.106374
Self-citationEffort and control of pain: a dilemma for patients and providers
Sturgeon, J. A., Jennings, M. B., & Trost, Z. (2026) · PAIN Reports · doi:10.1097/pr9.0000000000001468
Metadata
- Authors
- Ashar, Y. K., Gordon, A., Schubiner, H., Uipi, C., Knight, K., Anderson, Z., Carlisle, J., Polisky, L., Geuter, S., Flood, T. F., Kragel, P. A., Dimidjian, S., Lumley, M. A., & Wager, T. D.
- Affiliations
- University of Colorado Boulder (US)
- Pain Psychology Center, Los Angeles, California
- Ascension Providence Hospital (US)
- Panorama Orthopedics and Spine Center, Golden, Colorado
- Northwestern University (US)
- Johns Hopkins University (US)
- Brigham and Women's Hospital (US)
- Emory University (US)
- Wayne State University (US)
- Dartmouth College (US)
- Corresponding author
- Ashar, Yoni K.
- Wager, Tor D.
- ORCID
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2022-01-01
- Volume
- 79
- Issue
- 1
- Pages
- 13
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC8482298
- OpenAlex
- W3204387157
- Cited by
- 331
- References
- 82
- Citations by year
- 2026: 87 · 2025: 80 · 2024: 85 · 2023: 45 · 2022: 32
- FWCI
- 23.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- JAMA Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health (TL1TR002386)
- National Institute of Mental Health (R01MH076136)
- National Institute on Drug Abuse (R01DA035484)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Health Professions › Physical Therapy, Sports Therapy and Rehabilitation › Musculoskeletal pain and rehabilitation
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Keywords
- chronic back pain, pain beliefs, fear avoidance, placebo effect, psychological intervention, telemedicine, evoked pain, resting-state functional connectivity, therapeutic mechanisms, pain intensity, disability, treatment durability, fear-avoidance beliefs, pain catastrophizing, pain-related guilt, pain-related shame, pain-related hopelessness
- MeSH terms
- Adult, Back Pain, Disability Evaluation, Female, Humans, Male, Middle Aged, Pain, Treatment Outcome, Pain Management
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