Expression of the TRPV1 receptor differs in quiescent inflammatory bowel disease with or without abdominal pain.
OBJECTIVE
Transient receptor potential vanilloid type 1 (TRPV1) has been shown to play an important role in visceral hypersensitivity. A significant proportion of patients with inflammatory bowel disease (IBD) continue to complain of abdominal pain despite their disease being otherwise quiescent. We investigated TRPV1-immunoreactive fibres in rectosigmoid biopsies taken from such patients with correlation to abdominal pain severity.


METHODS
Rectosigmoid biopsies were collected from 20 patients with quiescent IBD fulfilling Rome II criteria for irritable bowel syndrome (IBS), from 20 asymptomatic patients with quiescent IBD and from 28 controls. Abdominal pain scores were recorded using a validated questionnaire. TRPV1- and neuronal marker protein gene product 9.5 (PGP 9.5)-expressing nerve fibres, and lymphocytes (CD3 and CD4) were quantified, following immunohistochemistry with specific antibodies. The biopsy findings were related to abdominal pain scores.


RESULTS
A significant 3.9-fold increase in median number of TRPV1-immunoreactive fibres was found in biopsies from patients with quiescent IBD with IBS symptoms when compared with controls (p<0.0001) and a 5-fold increase when compared with the asymptomatic quiescent IBD group (p=0.0003). In the IBD with IBS symptoms group, the total nerve fibres (PGP 9.5) did not differ from those in the asymptomatic IBD group (p=0.10) or the control group (p=0.33) and neither did the CD3 lymphocyte (asymptomatic IBD group p=0.17; controls p=0.88) or CD4 lymphocyte (asymptomatic IBD group p=0.39; controls p=0.97) counts. In stepwise multivariate linear regression analysis, only TRPV1-immunoreactive nerve fibres (R(2)=0.8; p<0.0001) were significantly related to the abdominal pain score.


CONCLUSIONS
Increased TRPV1 nerve fibres are seen in quiescent IBD with IBS-like symptoms together with a correlation to pain severity. TRPV1 may contribute to the pathophysiology of ongoing pain and visceral hypersensitivity in this group of patients, providing a potential therapeutic target.
Akbar
Ayesha
A
Department of Gastroenterology, Imperial College London, UK.
Yiangou
Yiangos
Y
Facer
Paul
P
Brydon
W G
WG
Walters
Julian R F
JR
Anand
Praveen
P
Ghosh
Subrata
S
D015746:Abdominal Pain / Q000209:etiology / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001007:Anxiety / Q000209:etiology; D015415:Biomarkers / Q000378:metabolism; D003863:Depression / Q000209:etiology; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000294:innervation; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism; D010147:Pain Measurement / Q000379:methods; D011788:Quality of Life; D050916:TRPV Cation Channels / Q000378:metabolism* / Q000502:physiology
D015415:Biomarkers; D018836:Inflammation Mediators; D039841:Leukocyte L1 Antigen Complex; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human