Effect of Pain Reprocessing Therapy vs Placebo and Usual Care for Patients With Chronic Back Pain: A Randomized Clinical Trial

Yoni K Ashar, Alan Gordon, Howard Schubiner, Christie Uipi, Karen Knight, Zachary Anderson, Judith Carlisle, Laurie Polisky, Stephan Geuter, Thomas F Flood, Philip A Kragel, Sona Dimidjian, Mark A Lumley, Tor D Wager, Yoni K Ashar, Alan Gordon, Howard Schubiner, Christie Uipi, Karen Knight, Zachary Anderson, Judith Carlisle, Laurie Polisky, Stephan Geuter, Thomas F Flood, Philip A Kragel, Sona Dimidjian, Mark A Lumley, Tor D Wager

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Ashar reports grants from the National Institutes of Health during the conduct of the study and personal fees from UnitedHealth Group, Lin Health, Inc, Pain Reprocessing Therapy Center, Inc, and Mental Health Partners of Boulder County outside the submitted work. Mr Gordon is a consultant with UnitedHealth Group, director of the Pain Psychology Center and the Pain Reprocessing Therapy Center, and is the author of the book The Way Out. Dr Schubiner is the co-owner of Freedom From Chronic Pain, Inc, earns book royalties for Unlearn Your Pain, Unlearn Your Anxiety and Depression and Hidden From View; serves as a consultant with UnitedHealth Group, Karuna Labs, and Curable Health; and receives personal fees from OVID Dx outside the submitted work. Mrs Uipi serves as a consultant for UnitedHealth Group. Dr Dimidjian reports being a co-founder of Mindful Noggin, Inc, and received royalties from Guilford Press and Wolters Kluwer as well as funding from The National Institutes of Health. Dr Lumley reports personal fees from CognifiSense, Inc, outside the submitted work. Dr Wager reports grants from the National Institutes of Health and the Foundation for the Study of the Therapeutic Encounter, and funding to support trainees from the Radiological Society of North America and the German Research Foundation; he is on the Scientific Advisory Board of Curable Health. No other disclosures were reported.

Figures

Figure 1.. CONSORT Participant Flow Diagram
Figure 1.. CONSORT Participant Flow Diagram
MRI indicates magnetic resonance imaging.
Figure 2.. Clinical Outcomes
Figure 2.. Clinical Outcomes
A, Shading indicates standard error. B, Dots represent individual participants; thick lines represent the group mean. C, Percentage of patients reporting pain scores of 0 or 1 of 10 (ie, pain-free or nearly pain-free) at posttreatment and at 1-year follow-up. PRT indicates pain reprocessing therapy.
Figure 3.. Effects of Treatment on Evoked…
Figure 3.. Effects of Treatment on Evoked and Spontaneous Back Pain and Related Brain Function
A, Error bars show standard error. B, Coordinates and statistics for activations provided in eTable 7 in Supplement 2; analyses conducted within a mask of regions of interest; eFigure 1 in Supplement 2. C, Decreased evoked pain-related activity was observed in anterior midcingulate (aMCC) and anterior prefrontal regions for PRT vs placebo and left anterior insula for PRT vs usual care. D, Error bars show standard error. E, PRT vs control conditions increased aPFC-seeded (red clusters) and aIns-seeded (green clusters) connectivity with primary somatosensory cortex (permutation test, P < .05). Inset shows seed regions, derived from evoked pain analyses; magenta outlines, PRT vs placebo; black outlines, PRT vs usual care. F, PRT vs usual care increased connectivity between an aMCC seed (yellow; derived from evoked back pain analyses) and the precuneus (orange). Connectivity analyses were conducted within primary somatosensory cortex and medial default mode network masks. aP < .001. bP < .05.

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