title: The unpleasantness of tonic pain is encoded by the insular cortex.
abstract: OBJECTIVE
  Muscle pain differs from skin pain with respect to quality, accuracy of localization, and unpleasantness. This study was conducted to identify the brain regions associated with the affective-motivational component of tonic skin and muscle pain.
  
  
  METHODS
  Forty healthy volunteers were investigated in three groups with different F-18 fluorodeoxyglucose PET activation scans. A verbal rating scale (VRS) was used to quantify pain intensity and unpleasantness. One group was investigated during painful infusion of an acidified phosphate buffer (pH 5.2) into either muscle or skin for 30 minutes. Muscle and skin infusions were adjusted to achieve pain intensity rating of VRS = 40. The second group received sham stimulation of muscle and skin by infusion of non-acidified phosphate buffer (pH 7.3 to 7.4, pain intensity = 0). The third group underwent only one PET scan without sensory stimulation.
  
  
  RESULTS
  Unpleasantness ratings were higher (VRS 38.3 vs 25.5) during IM compared to intracutaneous stimulation, despite the same pain intensity (VRS = 40). Sham stimulation revealed no pain or unpleasantness. Regional cerebral glucose metabolism during sham stimulation showed similar findings for intracutaneous and IM infusions with significant activations of the bilateral anterior cingulate, bilateral frontal (premotor) cortex, and the ipsilateral parietal operculum. The comparison of pain vs sham stimulation revealed activations of the bilateral insula for IM but not intracutaneous stimulation. The unpleasantness perception in skin and muscle stimulation was positively correlated to the bilateral insular metabolism.
  
  
  CONCLUSIONS
  The data suggest that the insula represents one main structure where the unpleasantness of tonic pain perception is encoded.
authors.affiliation: Department of Nuclear Medicine, Johannes Gutenberg-University Mainz, Mainz, Germany. schreckenberger@nuklear.klinik.uni-mainz.de
authors.forename: M
authors.initials: M
authors.lastname: Schreckenberger
authors.forename: T
authors.initials: T
authors.lastname: Siessmeier
authors.forename: A
authors.initials: A
authors.lastname: Viertmann
authors.forename: C
authors.initials: C
authors.lastname: Landvogt
authors.forename: H-G
authors.initials: HG
authors.lastname: Buchholz
authors.forename: R
authors.initials: R
authors.lastname: Rolke
authors.forename: R-D
authors.initials: RD
authors.lastname: Treede
authors.forename: P
authors.initials: P
authors.lastname: Bartenstein
authors.forename: F
authors.initials: F
authors.lastname: Birklein
mesh_terms: D000143:Acids / Q000009:adverse effects; D000208:Acute Disease; D000328:Adult; D001931:Brain Mapping; D002021:Buffers; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002908:Chronic Disease; D004644:Emotions / Q000502:physiology*; D005260:Female; D019788:Fluorodeoxyglucose F18; D007839:Functional Laterality / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D049268:Positron-Emission Tomography; D012016:Reference Values; D012867:Skin / Q000294:innervation / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000143:Acids; D002021:Buffers; D019788:Fluorodeoxyglucose F18; D005947:Glucose