title: Abdominal pain and the neurotrophic system in ulcerative colitis.
abstract: BACKGROUND
  We undertook a study to test the hypothesis that inflammation alters peripheral sensory mechanisms, thereby contributing to chronic abdominal pain in ulcerative colitis (UC).
  
  
  METHODS
  Patients with UC and healthy individuals rated abdominal pain using a visual analog scale and completed surveys describing anxiety or depression (Hospital Anxiety and Depression Score) and gastrointestinal symptoms (Rome III questionnaire). Patient age, sex, and severity of inflammation were determined. Rectal biopsies were processed using immunohistochemical techniques to assess nerve fiber density and real-time PCR to determine transcript expression of neurotrophins (nerve growth factor, glial cell-derived neurotrophic factor, artemin, neurturin), ion channels (transient receptor potential vanilloid type 1, transient receptor potential ankyrin 1) and inflammatory mediators (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, IL-10, IL-17).
  
  
  RESULTS
  A total of 77 patients with UC (27 female, 50 male) and 21 controls (10 female, 11 male) were enrolled. Patients with UC with pain had significantly higher depression scores than controls and patients with UC without pain (P < 0.05). There was no correlation between any of the inflammatory markers and pain scores. Visual analog scale pain scores significantly correlated with younger age, higher depression scores, increased expression of neurturin and decreased expression of transient receptor potential ankyrin 1 in the mucosa. Mucosal nerve fiber density did not correlate with any measures of inflammation or pain. Only higher depression scores independently predicted pain in UC (r > 0.5).
  
  
  CONCLUSIONS
  We did not observe changes in mucosal innervation and did not see a significant relationship between nerve fiber density, inflammatory mediators, neurotrophic factors, or mucosal ion channel expression and pain. In contrast, the importance of depression as the only independent predictor of pain ratings mirrors functional disorders, where central processes significantly contribute to symptom development and/or perpetuation.
authors.affiliation: *Department of Psychology, University of Alabama at Birmingham, Birmingham, Alabama; †Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; ‡Department of Neurosciences, University of Pittsburgh, Pittsburgh, Pennsylvania; §Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and ‖Department of Medicine, Division of Gastroenterology, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Deberry
authors.forename: Klaus
authors.initials: K
authors.lastname: Bielefeldt
authors.forename: Brian M
authors.initials: BM
authors.lastname: Davis
authors.forename: Eva M
authors.initials: EM
authors.lastname: Szigethy
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Hartman
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Coates
mesh_terms: D015746:Abdominal Pain / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001007:Anxiety / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000150:complications*; D003863:Depression / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D007473:Ion Channels; D009414:Nerve Growth Factors; D012333:RNA, Messenger