Intrinsic Brain Connectivity in Chronic Pain: A Resting-State fMRI Study in Patients with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) is commonly accompanied by pain that is discordant with the degree of peripheral pathology. Very little is known about the cerebral processes involved in pain processing in RA. Here we investigated resting-state brain connectivity associated with prolonged pain in RA. Methods: 24 RA subjects and 19 matched controls were compared with regard to both behavioral measures of pain perception and resting-resting state fMRI data acquired subsequently to fMRI sessions involving pain stimuli. The resting-state fMRI brain connectivity was investigated using 159 seed regions located in cardinal pain processing brain regions. Additional principal component based multivariate pattern analysis of the whole brain connectivity pattern was carried out in a data driven analysis to localize group differences in functional connectivity. Results: When RA patients were compared to controls, we observed significantly lower pain resilience for pressure on the affected finger joints (i.e., P50-joint) and an overall heightened level of perceived global pain in RA patients. Relative to controls, RA patients displayed increased brain connectivity predominately for the supplementary motor areas, mid-cingulate cortex, and the primary sensorimotor cortex. Additionally, we observed an increase in brain connectivity between the insula and prefrontal cortex as well as between anterior cingulate cortex and occipital areas for RA patients. None of the group differences in brain connectivity were significantly correlated with behavioral parameters. Conclusion: Our study provides experimental evidence of increased connectivity between frontal midline regions that are implicated in affective pain processing and bilateral sensorimotor regions in RA patients.

[1]  A. K. Jones,et al.  Reduced cortical responses to noxious heat in patients with rheumatoid arthritis , 1997, Annals of the rheumatic diseases.

[2]  D. Schacter,et al.  Correlated low-frequency BOLD fluctuations in the resting human brain are modulated by recent experience in category-preferential visual regions. , 2010, Cerebral cortex.

[3]  R. Poldrack.  Inferring Mental States from Neuroimaging Data: From Reverse Inference to Large-Scale Decoding , 2011, Neuron.

[4]  Mammo Muchie,et al.  Introduction to the Special Issue on: Building Capacity to Develop and Use Science, Technology and innovation Indicators , 2012 .

[5]  Thomas J. Schnitzer,et al.  Corticostriatal functional connectivity predicts transition to chronic back pain , 2012, Nature Neuroscience.

[6]  C. Opava,et al.  Higher pain sensitivity and lower muscle strength in postmenonpausal women with early rheumatoid arthritis compared with age-matched healthy women – a pilot study , 2013, Disability and rehabilitation.

[7]  Susan L. Whitfield-Gabrieli,et al.  Conn: A Functional Connectivity Toolbox for Correlated and Anticorrelated Brain Networks , 2012, Brain Connect..

[8]  Irene Tracey,et al.  Investigation into the neural correlates of emotional augmentation of clinical pain , 2008, NeuroImage.

[9]  Mark Jenkinson,et al.  Structural changes of the brain in rheumatoid arthritis. , 2012, Arthritis and rheumatism.

[10]  Ning Zhong,et al.  Changes in the brain intrinsic organization in both on-task state and post-task resting state , 2012, NeuroImage.

[11]  F. Arnett.  Revised criteria for the classification of rheumatoid arthritis. , 1990, Orthopedic nursing.

[12]  J. O'dell,et al.  State-of-the-art: rheumatoid arthritis , 2010, Annals of the rheumatic diseases.

[13]  G. Kersley.  Pain in the rheumatic diseases. , 1947, The Practitioner.

[14]  Peter Fransson,et al.  Fibromyalgia Is Associated with Decreased Connectivity Between Pain- and Sensorimotor Brain Areas , 2014, Brain Connect..

[15]  Thomas T. Liu,et al.  A component based noise correction method (CompCor) for BOLD and perfusion based fMRI , 2007, NeuroImage.

[16]  Markus Burgmer,et al.  Altered brain activity during pain processing in fibromyalgia , 2009, NeuroImage.

[17]  Anjali Krishnan,et al.  Cluster-extent based thresholding in fMRI analyses: Pitfalls and recommendations , 2014, NeuroImage.

[18]  B. Pfleiderer,et al.  Diagnostic classification based on functional connectivity in chronic pain: model optimization in fibromyalgia and rheumatoid arthritis. , 2014, Academic radiology.

[19]  Vitaly Napadow,et al.  What has functional connectivity and chemical neuroimaging in fibromyalgia taught us about the mechanisms and management of ‘centralized’ pain? , 2014, Arthritis Research & Therapy.

[20]  Anthony K. P. Jones,et al.  Role of Functional Brain Imaging in Understanding Rheumatic Pain , 2012, Current Rheumatology Reports.

[21]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[22]  Emma G Duerden,et al.  Localization of pain‐related brain activation: A meta‐analysis of neuroimaging data , 2013, Human brain mapping.

[23]  P. Hansson,et al.  Somatosensory perception and function of diffuse noxious inhibitory controls (DNIC) in patients suffering from rheumatoid arthritis , 2002, European journal of pain.

[24]  M. Prevoo,et al.  Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. , 1995, Arthritis and rheumatism.

[25]  Steven C. R. Williams,et al.  Evidence of dysfunctional pain inhibition in Fibromyalgia reflected in rACC during provoked pain , 2009, PAIN®.

[26]  M. Liang,et al.  The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. , 1988, Arthritis and rheumatism.

[27]  Richard E. Harris,et al.  Decreased intrinsic brain connectivity is associated with reduced clinical pain in fibromyalgia. , 2012, Arthritis and rheumatism.

[28]  Laura Blanco-Hinojo,et al.  The contribution of sensory system functional connectivity reduction to clinical pain in fibromyalgia , 2014, PAIN®.

[29]  D. Barch,et al.  Introduction to the special issue on reliability and replication in cognitive and affective neuroscience research , 2013, Cognitive, affective & behavioral neuroscience.

[30]  F. Wolfe,et al.  Patient Perceptions concerning Pain Management in the Treatment of Rheumatoid Arthritis , 2010, The Journal of international medical research.

[31]  Beatriz Luna,et al.  The nuisance of nuisance regression: Spectral misspecification in a common approach to resting-state fMRI preprocessing reintroduces noise and obscures functional connectivity , 2013, NeuroImage.

[32]  T. Schnitzer,et al.  Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits. , 2013, Brain : a journal of neurology.

[33]  Peter Fransson,et al.  Patients with fibromyalgia display less functional connectivity in the brain’s pain inhibitory network , 2012, Molecular pain.