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Visceral hypersensitivity in symptomatic diverticular disease and the role of neuropeptides and low grade inflammation
Author(s) -
Humes D. J.,
Simpson J.,
Smith J.,
Sutton P.,
Zaitoun A.,
Bush D.,
Bennett A.,
Scholefield J. H.,
Spiller R. C.
Publication year - 2012
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2011.01863.x
Subject(s) - medicine , asymptomatic , gastroenterology , diverticular disease , galanin , diverticulosis , barostat , diverticulitis , abdominal pain , substance p , neuropeptide , receptor , irritable bowel syndrome
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). Key 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 & Inferences Patients with symptomatic diverticular disease exhibit visceral hypersensitivity, and this may be mediated by ongoing low grade inflammation and upregulation of tachykinins.