Chronic pain is a widespread international health problem that imposes costs of over 600 billion dollars per year. This application focuses on fibromyalgia (FM), which is characterized by persistent, widespread body pain, with significant evidence of altered brain function. One of the few effective treatments for FM is cognitive-behavioral therapy (CBT), which has been shown to reduce pain intensity and pain-related disability, potentially via reductions in catastrophizing, an important psychosocial factor that plays a crucial role in shaping individual differences in pain- related outcomes. It is likely that brain mechanisms underpin the beneficial effects of lowered catastrophizing and reduced pain in FM, and CBT-produced decrements in catastrophizing may act to """"""""normalize"""""""" dysfunctional central nervous system pain processing. Our previous study in FM patients confirms that patients who are high in catastrophizing show enhanced pain-related activation in brain areas that process emotional aspects of pain (e.g., anterior insula and medial thalamus). In addition, catastrophizing was associated with altered pain-evoked functional connectivity between thalamus, anterior insula, and default mode network (DMN) structures such as medial prefrontal cortex. The DMN is a constellation of brain regions that mediate self- focused cognitive processing;our prior work has implicated altered resting-state functional connectivity between DMN and insula as a biomarker for clinical pain in FM. In our pilot study, a subset of FM patients was randomized to CBT or an active educational control condition. We found that CBT reduced catastrophizing and produced corresponding changes in brain activation and DMN connectivity. In the present proposal, we hypothesize that CBT-produced improvements in pain will be anticipated and mediated by reductions in catastrophizing and their associated effects on pain-related brain functioning. Participants with FM will be randomized to 8 weekly treatments with CBT or an education/attention control, and followed up for 6 months. Functional MRI data, including functional connectivity during both a resting and evoked deep- tissue pain state, will be collected at baseline, mid-treatment, and after the final treatment visit. We hypothesize that CBT will reduce catastrophizing early in treatment, resulting in adaptive changes in the brain's responses to an externally-applied noxious stimulus. These changes will then predict subsequent changes in patients'resting state connectivity in DMN and pain- relevant brain regions, which will underlie long-term improvements in clinical pain. Our overarching goal is to understand the neurobiological pathways by which CBT and reduced catastrophizing facilitate improvements in chronic pain;such information will help to refine biopsychosocial models of pain, identify potential non-responders early in treatment, and facilitate the enhancement of psychosocial interventions for chronic musculoskeletal pain.

Public Health Relevance

Chronic pain is a major public health problem and a leading cause of disability. Psychosocial treatments such as cognitive-behavioral therapy are effective long-term pain management approaches, but we know little about how they change the central nervous system's processing of pain-related information. This functional neuroimaging study will evaluate the brain mechanisms by which CBT reduces pain and improves quality of life in patients with fibromyalgia. Our long-term goal is to understand the neurobiological pathways that underlie successful psychosocial interventions for patients with chronic pain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR064367-01A1
Application #
8631674
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Serrate-Sztein, Susana
Project Start
2014-05-12
Project End
2019-04-30
Budget Start
2014-05-12
Budget End
2015-04-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
Smith, Shannon M; Dworkin, Robert H; Turk, Dennis C et al. (2017) The Potential Role of Sensory Testing, Skin Biopsy, and Functional Brain Imaging as Biomarkers in Chronic Pain Clinical Trials: IMMPACT Considerations. J Pain 18:757-777
Dworkin, Robert H; Edwards, Robert R (2017) Phenotypes and treatment response: it's difficult to make predictions, especially about the future. Pain 158:187-189
Lazaridou, Asimina; Kim, Jieun; Cahalan, Christine M et al. (2017) Effects of Cognitive-Behavioral Therapy (CBT) on Brain Connectivity Supporting Catastrophizing in Fibromyalgia. Clin J Pain 33:215-221
Song, Andrew H; Kucyi, Aaron; Napadow, Vitaly et al. (2017) Pharmacological Modulation of Noradrenergic Arousal Circuitry Disrupts Functional Connectivity of the Locus Ceruleus in Humans. J Neurosci 37:6938-6945
Toschi, Nicola; Kim, Jieun; Sclocco, Roberta et al. (2017) Motion sickness increases functional connectivity between visual motion and nausea-associated brain regions. Auton Neurosci 202:108-113
Schreiber, Kristin L; Loggia, Marco L; Kim, Jieun et al. (2017) Painful After-Sensations in Fibromyalgia are Linked to Catastrophizing and Differences in Brain Response in the Medial Temporal Lobe. J Pain 18:855-867
Garcia, Ronald G; Lin, Richard L; Lee, Jeungchan et al. (2017) Modulation of brainstem activity and connectivity by respiratory-gated auricular vagal afferent nerve stimulation in migraine patients. Pain 158:1461-1472
Ellingsen, D-M; Garcia, R G; Lee, J et al. (2017) Cyclic Vomiting Syndrome is characterized by altered functional brain connectivity of the insular cortex: A cross-comparison with migraine and healthy adults. Neurogastroenterol Motil 29:
Lee, Yvonne C; Massarotti, Elena; Edwards, Robert R et al. (2016) Effect of Milnacipran on Pain in Patients with Rheumatoid Arthritis with Widespread Pain: A Randomized Blinded Crossover Trial. J Rheumatol 43:38-45
Martel, M O; Olesen, A E; Jørgensen, D et al. (2016) Does catastrophic thinking enhance oesophageal pain sensitivity? An experimental investigation. Eur J Pain 20:1214-22

Showing the most recent 10 out of 33 publications