title: The somatosensory link in fibromyalgia: functional connectivity of the primary somatosensory cortex is altered by sustained pain and is associated with clinical/autonomic dysfunction.
abstract: OBJECTIVE
  Fibromyalgia (FM) is a chronic functional pain syndrome characterized by widespread pain, significant pain catastrophizing, sympathovagal dysfunction, and amplified temporal summation for evoked pain. While several studies have demonstrated altered resting brain connectivity in FM, studies have not specifically probed the somatosensory system and its role in both somatic and nonsomatic FM symptoms. Our objective was to evaluate resting primary somatosensory cortex (S1) connectivity and to explore how sustained, evoked deep tissue pain modulates this connectivity.
  
  
  METHODS
  We acquired functional magnetic resonance imaging and electrocardiography data on FM patients and healthy controls during rest (the rest phase) and during sustained mechanical pressure-induced pain over the lower leg (the pain phase). Functional connectivity associated with different S1 subregions was calculated, while S1(leg) connectivity (representation of the leg in the primary somatosensory cortex) was contrasted between the rest phase and the pain phase and was correlated with clinically relevant measures in FM.
  
  
  RESULTS
  During the rest phase, FM patients showed decreased connectivity between multiple ipsilateral and cross-hemispheric S1 subregions, which was correlated with clinical pain severity. Compared to the rest phase, the pain phase produced increased S1(leg) connectivity to the bilateral anterior insula in FM patients, but not in healthy controls. Moreover, in FM patients, sustained pain-altered S1(leg) connectivity to the anterior insula was correlated with clinical/behavioral pain measures and autonomic responses.
  
  
  CONCLUSIONS
  Our study demonstrates that both somatic and nonsomatic dysfunction in FM, including clinical pain, pain catastrophizing, autonomic dysfunction, and amplified temporal summation, are closely linked with the degree to which evoked deep tissue pain alters S1 connectivity to salience/affective pain-processing regions. Additionally, diminished connectivity between S1 subregions during the rest phase in FM may result from ongoing widespread clinical pain.
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA.|Division of Medical Research, Korea Institute of Oriental Medicine, Daejeon, Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA.|Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School (HMS), Chestnut Hill, MA, USA.
authors.forename: Marco L
authors.initials: ML
authors.lastname: Loggia
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School (HMS), Chestnut Hill, MA, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Cahalan
authors.affiliation: Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan Health Center, Ann Arbor, MI, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Harris
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA.|Somatosensory and Autonomic Therapy Research, Institute for Neuroradiology, Hannover Medical School, Hannover, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Beissner
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA.|Masira Research Institute, School of Medicine, Universidad de Santander, Bucaramanga, Colombia.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Garcia
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA.|Division of Medical Research, Korea Institute of Oriental Medicine, Daejeon, Korea.
authors.forename: Hyungjun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Departments of Anesthesiology and Psychiatry, University of Pittsburgh School of Medicine, PA, USA.
authors.forename: Ajay D
authors.initials: AD
authors.lastname: Wasan
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School (HMS), Chestnut Hill, MA, USA.|Department of Psychiatry, Brigham and Women's Hospital, HMS, Boston, MA, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Edwards
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA.|Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School (HMS), Chestnut Hill, MA, USA.|Department of Biomedical Engineering, College of Electronics and Information, Kyung Hee University, Yongin, Korea.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Napadow
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000503:physiopathology*; D004562:Electrocardiography; D005260:Female; D005356:Fibromyalgia / Q000150:complications / Q000503:physiopathology*; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology*; D010146:Pain / Q000150:complications / Q000503:physiopathology*; D010147:Pain Measurement; D011312:Pressure; D054969:Primary Dysautonomias / Q000150:complications / Q000503:physiopathology*; D012720:Severity of Illness Index; D013003:Somatosensory Cortex / Q000503:physiopathology*