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Cognitive-Behavioral Therapy Increases Prefrontal Cortex Gray Matter in Patients With Chronic Pain
Open accessAbstract
Unlabelled Several studies have reported reduced cerebral gray matter (GM) volume or density in chronic pain conditions, but there is limited research on the plasticity of the human cortex in response to psychological interventions. We investigated GM changes after cognitive-behavioral therapy (CBT) in patients with chronic pain. We used voxel-based morphometry to compare anatomic magnetic resonance imaging scans of 13 patients with mixed chronic pain types before and after an 11-week CBT treatment and to 13 healthy control participants. CBT led to significant improvements in clinical measures. Patients did not differ from healthy controls in GM anywhere in the brain. After treatment, patients had increased GM in the bilateral dorsolateral prefrontal, posterior parietal, subgenual anterior cingulate/orbitofrontal, and sensorimotor cortices, as well as hippocampus, and reduced GM in supplementary motor area. In most of these areas showing GM increases, GM became significantly higher than in controls. Decreased pain catastrophizing was associated with increased GM in the left dorsolateral prefrontal and ventrolateral prefrontal cortices, right posterior parietal cortex, somatosensory cortex, and pregenual anterior cingulate cortex. Although future studies with additional control groups will be needed to determine the specific roles of CBT on GM and brain function, we propose that increased GM in the prefrontal and posterior parietal cortices reflects greater top-down control over pain and cognitive reappraisal of pain, and that changes in somatosensory cortices reflect alterations in the perception of noxious signals.Perspective An 11-week CBT intervention for coping with chronic pain resulted in increased GM volume in prefrontal and somatosensory brain regions, as well as increased dorsolateral prefrontal volume associated with reduced pain catastrophizing. These results add to mounting evidence that CBT can be a valuable treatment option for chronic pain.
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“Notably there was increased functional connectivity between the DLPFC and the periaqueductal gray – an opioid rich brainstem region involved in descending pain modulation91”
From The dorsolateral prefrontal cortex in acute and chronic pain (2017) · cites this paper as [91]
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“Another study investigating the neural underpinnings of effective pain management with cognitive behavioral training in a mixed chronic pain population reported increased left DLPFC GMV, which correlated with reduction in pain catastrophizing91”
From The dorsolateral prefrontal cortex in acute and chronic pain (2017) · cites this paper as [91]
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“More details about the clinical measures can be found in Naylor et al.54”
BackgroundMethodInfluentialSelf-citationPrefrontal influences upon the midbrain: A possible route for pain modulation
Hardy, S. G. P., & Haigler, H. J. (1985) · Brain Research · doi:10.1016/0006-8993(85)90094-0 · Cited by 106
Dissociated Grey Matter Changes with Prolonged Addiction and Extended Abstinence in Cocaine Users
Connolly, C. G., Bell, R. P., Foxe, J. J., & Garavan, H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059645 · Cited by 100
Expecting unpleasant stimuli–an fMRI study
Herwig, U., Abler, B., Walter, H., & Erk, S. (2007) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2006.02.007 · Cited by 92
Rogers, W. H., Wittink, H. M., Wagner, A. K., Cynn, D. J., & Carr, D. B. (2000) · Pain Medicine · doi:10.1046/j.1526-4637.2000.99102.x · Cited by 90 · cited 1×
“The TOPS provides 3 measures of patients’ functioning and disability: 1) the SF-36 Mental Health Composite, 2) the SF-36 Physical Health Composite, and 3) the TOPS Total Pain Experience scale.(62,63,75)”
MethodAbnormal gray matter aging in chronic pain patients
Moayedi, M., Weissman‐Fogel, I., Salomons, T. V., Crawley, A. P., Goldberg, M. B., Freeman, B. V., Tenenbaum, H. C., & Davis, K. D. (2012) · Brain Research · doi:10.1016/j.brainres.2012.03.040 · Cited by 87 · cited 6×
“Although the majority of these studies reported decreased GM in patients, some reported increased GM.50 Furthermore, some studies reported relatively few regional differences in GM between patients and controls,12 and at least 1 reported no differences at all.16 In the current study, patients did not have significantl…”
BackgroundResultInfluentialMulti-site voxel-based morphometry — Not quite there yet
Focke, N. K., Helms, G., Kaspar, S., Diederich, C., Tóth, V., Dechent, P., Mohr, A., & Paulus, W. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.02.029 · Cited by 87
The neurobiology of successful abstinence
Garavan, H., Brennan, K., Hester, R., & Whelan, R. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.01.029 · Cited by 76 · cited 1×
“Such a finding of increase in GM beyond the normal levels of healthy controls has been reported in recovery from addiction,(11) and a recent review of the literature suggests that the increase in PFC GM and functional activity reported in several studies is related to an increase in cognitive control required to maint…”
ResultUsing the “TOPS,” an Outcomes Instrument for Multidisciplinary Outpatient Pain Treatment
Rogers, W. H., Wittink, H. M., Ashburn, M. A., Cynn, D. J., & Carr, D. B. (2000) · Pain Medicine · doi:10.1046/j.1526-4637.2000.99101.x · Cited by 72
Group treatment for pain and discomfort
Basler, H.-D. (1993) · Patient Education and Counseling · doi:10.1016/0738-3991(93)90130-o · Cited by 43 · cited 1×
“Practicing these skills improves coping with pain and often reduces pain in clinical trials.(4,5,35,36,47,51) We hypothesized that prefrontal brain regions involved in the experience and modulation of pain, which have documented structural abnormalities in chronic pain patients, will normalize following CBT and that t…”
BackgroundAutomated telephone as an adjunct for the treatment of chronic pain: a pilot study
Naylor, M. R., Helzer, J. E., Naud, S. J., & Keefe, F. J. (2002) · Journal of Pain · doi:10.1054/jpai.2002.129563 · Cited by 43 · cited 1×
“An in-depth description of the program has been previously reported.(53,54)”
MethodSelf-citationVariations in Brain Gray Matter Associated with Chronic Pain
Wood, P. B. (2010) · Current Rheumatology Reports · doi:10.1007/s11926-010-0129-7 · Cited by 26
Cited by
Sorted by citations
The role of psychosocial processes in the development and maintenance of chronic pain
Edwards, R. R., Dworkin, R. H., Sullivan, M. D., Turk, D. C., & Wasan, A. D. (2016) · The Journal of Pain · doi:10.1016/j.jpain.2016.01.001 · Cited by 954
“Finally, psychosocial and behavioral interventions that target cognitive processes have been shown to reverse these functional and structural brain changes over the course of just months.(204,205)”
Role of the Prefrontal Cortex in Pain Processing
Ong, W., Stohler, C. S., & Herr, D. R. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1130-9 · Cited by 824
“Interestingly, cognitive behavioral therapy has also been found to result in increased graymatter in patient with chronic pain [277].”
BackgroundThe dorsolateral prefrontal cortex in acute and chronic pain
Seminowicz, D. A., & Moayedi, M. (2017) · The Journal of Pain · doi:10.1016/j.jpain.2017.03.008 · Cited by 502
Self-citationPsychological processing in chronic pain: a neural systems approach
Simons, L. E., Elman, I., & Borsook, D. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.12.006 · Cited by 359
Brain changes associated with cognitive and emotional factors in chronic pain: A systematic review
Malfliet, A., Coppieters, I., Van Wilgen, P., Kregel, J., De Pauw, R., Dolphens, M., & Ickmans, K. (2017) · European Journal of Pain · doi:10.1002/ejp.1003 · Cited by 342
“…and gray matter morphology, resting state functional connectivity, and task-related functional brain activation (Gracely et al., 2004; Lloyd et al., 2008, 2014; Blankstein et al., 2010; Burgmer et al., 2011; Seminowicz et al., 2013; Kucyi et al., 2014; Gupta et al., 2015; Loggia et al., 2015).”
BackgroundInfluential
Metadata
- Authors
- Seminowicz, D. A., Shpaner, M., Keaser, M. L., Krauthamer, G. M., Mantegna, J., Dumas, J. A., Newhouse, P. A., Filippi, C. G., Keefe, F. J., & Naylor, M. R.
- Affiliations
- University of Maryland, Baltimore (US)
- University of Vermont (US)
- Duke University (US)
- Corresponding author
- Naylor, Magdalena R.
- Venue
- The Journal of Pain
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 14
- Issue
- 12
- Pages
- 1573-1584
- ISSN
- 1526-5900 (ISSN-L)
- PMC
- PMC3874446
- OpenAlex
- W2081653089
- Cited by
- 305
- References
- 82
- Citations by year
- 2026: 12 · 2025: 33 · 2024: 28 · 2023: 25 · 2022: 26 · 2021: 26 · 2020: 23 · 2019: 29 · 2018: 28 · 2017: 24 · 2016: 25 · 2015: 17 · 2014: 9
- FWCI
- 21.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Pain (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Centre d'Imagerie BioMédicale
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR059674, R01AR052131, R21AR055716)
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Keywords
- cognitive behavioral therapy, chronic pain, gray matter volume, prefrontal cortex, dorsolateral prefrontal cortex, posterior parietal cortex, pain catastrophizing, somatosensory cortex, supplementary motor area, hippocampus, neuroplasticity, psychological intervention
- MeSH terms
- Adaptation, Psychological, Adult, Aged, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Pain Measurement, Cognitive Behavioral Therapy, Prefrontal Cortex, Young Adult, Chronic Pain
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