title: The analgesic effect of pregabalin in patients with chronic pain is reflected by changes in pharmaco-EEG spectral indices.
abstract: OBJECTIVE
  To identify electroencephalographic (EEG) biomarkers for the analgesic effect of pregabalin in patients with chronic visceral pain.
  
  
  METHODS
  This was a double-blind, placebo-controlled study in 31 patients suffering from visceral pain due to chronic pancreatitis. Patients received increasing doses of pregabalin (75mg-300mg twice a day) or matching placebo during 3 weeks of treatment. Pain scores were documented in a diary based on a visual analogue scale. In addition, brief pain inventory-short form (BPI) and quality of life questionnaires were collected prior to and after the study period. Multi-channel resting EEG was recorded before treatment onset and at the end of the study. Changes in EEG spectral indices were extracted, and individual changes were classified by a support vector machine (SVM) to discriminate the pregabalin and placebo responses. Changes in individual spectral indices and pain scores were correlated.
  
  
  RESULTS
  Pregabalin increased normalized intensity in low spectral indices, most prominent in the theta band (3.5-7.5Hz), difference of -3.18, 95% CI -3.57, -2.80; P= 0.03. No changes in spectral indices were seen for placebo. The maximum difference between pregabalin and placebo treated patients was seen in the parietal region, with a classification accuracy of 85.7% (P= 0.009). Individual changes in EEG indices were correlated with changes in pain diary (P= 0.04) and BPI pain composite scores (P= 0.02).
  
  
  CONCLUSIONS
  Changes in spectral indices caused by slowing of brain oscillations were identified as a biomarker for the central analgesic effect of pregabalin. The developed methodology may provide perspectives to assess individual responses to treatment in personalized medicine.
authors.affiliation: Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
authors.forename: Carina
authors.initials: C
authors.lastname: Graversen
authors.forename: Søren S
authors.initials: SS
authors.lastname: Olesen
authors.forename: Anne E
authors.initials: AE
authors.lastname: Olesen
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Steimle
authors.forename: Dario
authors.initials: D
authors.lastname: Farina
authors.forename: Oliver H G
authors.initials: OH
authors.lastname: Wilder-Smith
authors.forename: Stefan A W
authors.initials: SA
authors.lastname: Bouwense
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Asbjørn M
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000328:Adult; D000700:Analgesics / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D050500:Pancreatitis, Chronic / Q000188:drug therapy*; D000069583:Pregabalin; D011788:Quality of Life; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D059265:Visceral Pain / Q000188:drug therapy*; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid