Sensitivity testing in irritable bowel syndrome with rectal capsaicin stimulations: role of TRPV1 upregulation and sensitization in visceral hypersensitivity?

Objectives: Abnormal pain perception or visceral hypersensitivity (VH) is considered important to be an important mechanism underlying symptoms in a subgroup of irritable bowel syndrome (IBS) patients. Increased TRPV1 expression in rectal biopsies of IBS patients suggests a potentially important role for this nociceptor in the pathophysiology of IBS. Evidence underscoring the involvement of TRPV1 in visceral perception in IBS however is lacking. The objective of this study was to evaluate the role of TRPV1 in visceral hypersensitivity to rectal distension and clinical symptoms in patients with IBS. Methods: 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 mmHg above minimal distension pressure. 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 100mm visual analogue scale (VAS). TRPV1 expression in rectal biopsies was determined by immunohistochemistry and Real-Time PCR. Results: 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 to normosensitive patients (ns-IBS) and HVs. Increased pain perception was significantly associated with symptoms scores of abdominal pain, loose stools and stool frequency. However, rectal TRPV1 expression was similar in VH-IBS, ns-IBS and HVs on both mRNA and protein expression level. TRPV1 expression levels did not correlate with pain perception to capsaicin or clinical symptoms in IBS patients or the subgroups. Anxiety experienced during the experimental procedure was enhanced in VH-IBS patients, but not ns-IBS or HVs. Conclusions: IBS patients with VH to rectal distension reveal increased pain perception to rectal application of capsaicin and an increased anxiety response. However, no increased mRNA or protein expression of TRPV1 could be detected in the rectal mucosa. Based on these findings, we speculate that in patients with IBS, TRPV1 sensitization rather than upregulation of TRPV1 may be involved in VH, besides a potential role of central factors.status: publishe