title: Visceral hypersensitivity in symptomatic diverticular disease and the role of neuropeptides and low grade inflammation.
abstract: BACKGROUND
  Recurrent abdominal pain is reported by a third of patients with diverticulosis, particularly those with previous episodes of acute diverticulitis. The current understanding of the etiology of this pain is poor. Our aim was to assess visceral sensitivity in patients with diverticular disease and its association with markers of previous inflammation and neuropeptides.
  
  
  METHODS
  Patients with asymptomatic and symptomatic diverticular disease underwent a flexible sigmoidoscopy and biopsy followed 5-10 days later by visceral sensitivity testing with barostat-mediated rectal distension. Inflammation was assessed by staining of serotonin (5HT) and CD3 positive cells. mRNA levels of tumor necrosis factor alpha (TNF α) and interleukin-6 (IL-6) were quantitated using RT-PCR. Neuropeptide expression was assessed from percentage area staining with substance P (SP) and mRNA levels of the neurokinin 1 & 2 receptors (NK1 & NK2), and galanin 1 receptor (GALR1).
  
  
  RESULTS
  Thirteen asymptomatic and 12 symptomatic patients were recruited. The symptomatic patients had a lower first reported threshold to pain (28.4 mmHg i.q.r 25.0-36.0) than the asymptomatic patients (47 mmHg i.q.r 36.0-52.5, P < 0.001). Symptomatic patients had a higher median overall pain rating for the stimuli than the asymptomatic patients (P < 0.02). Symptomatic patients had greater median relative expression of NK1 and TNF alpha mRNA compared with asymptomatic patients. There was a significant correlation between barostat VAS pain scores and NK 1 expression (Figure 4, r(2) 0.54, P < 0.02).
  
  
  CONCLUSIONS
  Patients with symptomatic diverticular disease exhibit visceral hypersensitivity, and this may be mediated by ongoing low grade inflammation and upregulation of tachykinins.
authors.affiliation: Nottingham Digestive Disease Centre and Biomedical Research Unit, Nottingham University Hospital NHS Trust, Nottingham, UK. david.humes@nottingham.ac.uk
authors.forename: D J
authors.initials: DJ
authors.lastname: Humes
authors.forename: J
authors.initials: J
authors.lastname: Simpson
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: P
authors.initials: P
authors.lastname: Sutton
authors.forename: A
authors.initials: A
authors.lastname: Zaitoun
authors.forename: D
authors.initials: D
authors.lastname: Bush
authors.forename: A
authors.initials: A
authors.lastname: Bennett
authors.forename: J H
authors.initials: JH
authors.lastname: Scholefield
authors.forename: R C
authors.initials: RC
authors.lastname: Spiller
mesh_terms: D015746:Abdominal Pain / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D004239:Diverticulitis, Colonic / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D043963:Diverticulosis, Colonic / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006941:Hyperesthesia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000096:biosynthesis*; D017288:Pain Threshold / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D018013:Receptors, Neuropeptide / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014781:Viscera / Q000378:metabolism / Q000473:pathology
chemical_list: D009479:Neuropeptides; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide