title: Patients with fibromyalgia display less functional connectivity in the brain's pain inhibitory network.
abstract: BACKGROUND
  There is evidence for augmented processing of pain and impaired endogenous pain inhibition in Fibromyalgia syndrome (FM). In order to fully understand the mechanisms involved in FM pathology, there is a need for closer investigation of endogenous pain modulation. In the present study, we compared the functional connectivity of the descending pain inhibitory network in age-matched FM patients and healthy controls (HC).We performed functional magnetic resonance imaging (fMRI) in 42 subjects; 14 healthy and 28 age-matched FM patients (2 patients per HC), during randomly presented, subjectively calibrated pressure pain stimuli. A seed-based functional connectivity analysis of brain activity was performed. The seed coordinates were based on the findings from our previous study, comparing the fMRI signal during calibrated pressure pain in FM and HC: the rostral anterior cingulate cortex (rACC) and thalamus.
  
  
  RESULTS
  FM patients required significantly less pressure (kPa) to reach calibrated pain at 50 mm on a 0-100 visual analogue scale (p < .001, two-tailed). During fMRI scanning, the rACC displayed significantly higher connectivity to the amygdala, hippocampus, and brainstem in healthy controls, compared to FM patients. There were no regions where FM patients showed higher rACC connectivity. Thalamus showed significantly higher connectivity to the orbitofrontal cortex in healthy controls but no regions showed higher thalamic connectivity in FM patients.
  
  
  CONCLUSIONS
  Patients with FM displayed less connectivity within the brain's pain inhibitory network during calibrated pressure pain, compared to healthy controls. The present study provides brain-imaging evidence on how brain regions involved in homeostatic control of pain are less connected in FM patients. It is possible that the dysfunction of the descending pain modulatory network plays an important role in maintenance of FM pain and our results may translate into clinical implications by using the functional connectivity of the pain modulatory network as an objective measure of pain dysregulation.
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, USA. karinj@nmr.mgh.harvard.edu
authors.forename: Karin B
authors.initials: KB
authors.lastname: Jensen
authors.forename: Rita
authors.initials: R
authors.lastname: Loitoile
authors.forename: Eva
authors.initials: E
authors.lastname: Kosek
authors.forename: Frank
authors.initials: F
authors.lastname: Petzke
authors.forename: Serena
authors.initials: S
authors.lastname: Carville
authors.forename: Peter
authors.initials: P
authors.lastname: Fransson
authors.forename: Hanke
authors.initials: H
authors.lastname: Marcus
authors.forename: Steven C R
authors.initials: SC
authors.lastname: Williams
authors.forename: Ernest
authors.initials: E
authors.lastname: Choy
authors.forename: Yves
authors.initials: Y
authors.lastname: Mainguy
authors.forename: Olivier
authors.initials: O
authors.lastname: Vitton
authors.forename: Richard H
authors.initials: RH
authors.lastname: Gracely
authors.forename: Randy
authors.initials: R
authors.lastname: Gollub
authors.forename: Martin
authors.initials: M
authors.lastname: Ingvar
authors.forename: Jian
authors.initials: J
authors.lastname: Kong
mesh_terms: D000328:Adult; D000679:Amygdala / Q000502:physiology; D001921:Brain / Q000502:physiology*; D001933:Brain Stem / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D005356:Fibromyalgia / Q000503:physiopathology*; D006179:Gyrus Cinguli / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D010146:Pain / Q000503:physiopathology