title: Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia.
abstract: OBJECTIVE
  Fibromyalgia (FM) is a chronic widespread pain condition that is thought to arise from augmentation of central neural activity. Glutamate (Glu) is an excitatory neurotransmitter that functions in pain-processing pathways. This study was carried out to investigate the relationship between changing levels of Glu within the insula and changes in multiple pain domains in patients with FM.
  
  
  METHODS
  Ten patients with FM underwent 2 sessions of proton magnetic resonance spectroscopy (H-MRS) and 2 sessions of functional magnetic resonance imaging (FMRI), each conducted before and after a nonpharmacologic intervention to reduce pain. During H-MRS, the anterior and posterior insular regions were examined separately using single-voxel spectroscopy. The levels of Glu and other metabolites were estimated relative to levels of creatine (Cr) (e.g., the Glu/Cr ratio). During FMRI, painful pressures were applied to the thumbnail to elicit neuronal activation. Experimental pressure-evoked pain thresholds and clinical pain ratings (on the Short Form of the McGill Pain Questionnaire [SF-MPQ]) were also assessed prior to each imaging session
  
  
  RESULTS
  Both experimental pain (P = 0.047 versus pretreatment) and SF-MPQ-rated clinical pain (P = 0.043 versus pretreatment) were reduced following treatment. Changes from pre- to posttreatment in Glu/Cr were negatively correlated with changes in experimental pain thresholds (r = -0.95, P < 0.001) and positively correlated with changes in clinical pain (r = 0.85, P = 0.002). Changes in the FMRI-determined blood oxygenation level-dependent effect (a measure of neural activation) were positively correlated with changes in Glu/Cr within the contralateral insula (r = 0.81, P = 0.002).
  
  
  CONCLUSIONS
  Changes in Glu levels within the insula are associated with changes in multiple pain domains in patients with FM. Thus, H-MRS data may serve as a useful biomarker and surrogate end point for clinical trials of FM.
authors.affiliation: University of Michigan, Chronic Pain and Fatigue Research Center, Ann Arbor, MI 48106, USA. reharris@med.umich.edu
authors.forename: Richard E
authors.initials: RE
authors.lastname: Harris
authors.forename: Pia C
authors.initials: PC
authors.lastname: Sundgren
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Pang
authors.forename: Michael
authors.initials: M
authors.lastname: Hsu
authors.forename: Myria
authors.initials: M
authors.lastname: Petrou
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Samuel A
authors.initials: SA
authors.lastname: McLean
authors.forename: Richard H
authors.initials: RH
authors.lastname: Gracely
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Clauw
mesh_terms: D015670:Acupuncture Therapy / Q000379:methods; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005356:Fibromyalgia / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D010146:Pain / Q000378:metabolism* / Q000473:pathology; D059408:Pain Management; D012720:Severity of Illness Index; D016037:Single-Blind Method
chemical_list: D015415:Biomarkers; D018698:Glutamic Acid