title: Sensitivity testing in irritable bowel syndrome with rectal capsaicin stimulations: role of TRPV1 upregulation and sensitization in visceral hypersensitivity?
abstract: OBJECTIVE
  Abnormal pain perception or visceral hypersensitivity (VH) is considered to be an important mechanism underlying symptoms in a subgroup of irritable bowel syndrome (IBS) patients. Increased TRPV1 (transient receptor potential cation channel subfamily V member 1) expression in rectal biopsies of IBS patients suggests a potentially important role for this nociceptor in the pathophysiology of IBS. However, evidence underscoring the involvement of TRPV1 in visceral perception in IBS is lacking. The objective of this study was to evaluate the role of TRPV1 in VH to rectal distension and clinical symptoms in patients with IBS.
  
  
  METHODS
  A total of 48 IBS patients and 25 healthy volunteers (HVs) were invited to undergo subsequent assessment of sensitivity to rectal distensions and rectal capsaicin applications. Visceral sensitivity was evaluated by rectal distension at 3, 9, and 21 mm Hg above minimal distension pressure (MDP). Capsaicin was applied to the rectal mucosa (0.01%, 0.1%, or solvent only in random order). Visceral sensations (urge to defecate, pain, burning, and warmth sensation) were scored on a 100-mm visual analog scale (VAS). TRPV1 expression in rectal biopsies was determined by immunohistochemistry and real-time PCR.
  
  
  RESULTS
  A total of 23 IBS patients (48%) were hypersensitive to rectal distensions (VH-IBS). A concentration-dependent increase of urge and pain perception was present in HVs and IBS patients during capsaicin 0.01 and 0.1% applications. VH-IBS patients experienced a significantly increased perception of pain, but not urge, during capsaicin applications compared with normosensitive patients (ns-IBS) and HVs. Increased pain perception was significantly associated with anxiety and VH, symptoms scores of abdominal pain, loose stools, and stool frequency. Anxiety experienced during the experimental procedure was enhanced in VH-IBS patients but not in ns-IBS or HVs. However, rectal TRPV1 expression was similar in VH-IBS, ns-IBS, and HVs on both mRNA and protein expression levels. TRPV1 expression levels did not correlate with pain perception to capsaicin or clinical symptoms in IBS patients or the subgroups.
  
  
  CONCLUSIONS
  IBS patients with VH to rectal distension reveal increased pain perception to rectal application of capsaicin, as well as an increased anxiety response. No evidence for TRPV1 upregulation could be demonstrated. As both VH and anxiety are independently associated with increased pain perception to rectal capsaicin application, our data suggest that both peripheral and central factors are involved, with increased receptor sensitivity as a speculative possibility.
authors.affiliation: 1] Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium [2] These authors contributed equally to this work.
authors.forename: Sander J M
authors.initials: SJ
authors.lastname: van Wanrooij
authors.affiliation: 1] Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium [2] These authors contributed equally to this work.
authors.forename: Mira M
authors.initials: MM
authors.lastname: Wouters
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium.
authors.forename: Lukas
authors.initials: L
authors.lastname: Van Oudenhove
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium.
authors.forename: Winde
authors.initials: W
authors.lastname: Vanbrabant
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Mondelaers
authors.affiliation: Department of Human Biology, TU Munchen, Freising, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kollmann
authors.affiliation: Department of Human Biology, TU Munchen, Freising, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Kreutz
authors.affiliation: Department of Human Biology, TU Munchen, Freising, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schemann
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium.
authors.forename: Guy E
authors.initials: GE
authors.lastname: Boeckxstaens
mesh_terms: D015746:Abdominal Pain / Q000175:diagnosis / Q000209:etiology; D000328:Adult; D001007:Anxiety / Q000209:etiology; D001706:Biopsy; D002211:Capsaicin; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D008297:Male; D059225:Nociception / Q000502:physiology; D009619:Nociceptors / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology / Q000523:psychology; D012007:Rectum / Q000294:innervation / Q000473:pathology; D018689:Sensory System Agents; D050916:TRPV Cation Channels / Q000819:agonists / Q000235:genetics; D015854:Up-Regulation
chemical_list: D018689:Sensory System Agents; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D002211:Capsaicin