title: Association of Alterations in Gray Matter Volume With Reduced Evoked-Pain Connectivity Following Short-Term Administration of Pregabalin in Patients With Fibromyalgia.
abstract: Pregabalin (PGB) is an α2 δ calcium-channel subunit ligand that has previously been shown to reduce chronic pain in multiple conditions. Preclinical studies indicate that PGB may down-regulate brain glutamate release while also inhibiting astrocyte induction of glutamatergic synapse formation, and recent clinical findings support the notion that PGB modulates glutamatergic activity and functional brain connectivity in order to produce analgesia. The present study was undertaken to examine concurrent changes in brain gray matter volume (GMV) or evoked-pain connectivity in humans receiving PGB.
  
  
  
  Sixteen female fibromyalgia patients participated in a randomized double-blind 2-period crossover study of PGB versus placebo. Before and after each period, patients underwent high-resolution structural and evoked pressure-pain functional brain imaging. GMV was analyzed using voxel-based morphometry, and functional connectivity during evoked pressure-pain was assessed.
  
  
  
  PGB administration significantly reduced GMV within the posterior insula bilaterally, whereas there were no significant changes in insular GMV following placebo treatment. GMV reductions in the medial frontal gyrus were also observed when comparing PGB versus placebo treatment, and were associated with reduced clinical pain. These reductions in insular GMV were associated with concomitant reductions in connectivity to the default mode network, which was also associated with reduced clinical pain.
  
  
  
  Short-term PGB treatment altered brain structure and evoked-pain connectivity, and these decreases were associated with reduced clinical pain. We speculate that these fairly rapid changes in GMV may be related to brain neuroplasticity. It is unknown whether these effects are generalizable to other chronic pain states.
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Tudor
authors.initials: T
authors.lastname: Puiu
authors.affiliation: University of Michigan, Ann Arbor, and University of Colorado Denver.
authors.forename: Anson E
authors.initials: AE
authors.lastname: Kairys
authors.affiliation: Pfizer Global Research and Development, Groton, Connecticut.
authors.forename: Lynne
authors.initials: L
authors.lastname: Pauer
authors.affiliation: Ruhr University Bochum, Bochum, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmidt-Wilcke
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Eric
authors.initials: E
authors.lastname: Ichesco
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Johnson P
authors.initials: JP
authors.lastname: Hampson
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Napadow
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Clauw
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Harris
mesh_terms: D000328:Adult; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005356:Fibromyalgia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D066128:Gray Matter / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D009929:Organ Size / Q000187:drug effects; D000069583:Pregabalin / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000700:Analgesics; D000069583:Pregabalin
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