Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain.
OBJECTIVE
The capsaicin receptor TRPV1 (transient receptor potential vanilloid type-1) may play an important role in visceral pain and hypersensitivity states. In irritable bowel syndrome (IBS), abdominal pain is a common and distressing symptom where the pathophysiology is still not clearly defined. TRPV1-immunoreactive nerve fibres were investigated in colonic biopsies from patients with IBS, and this was related to abdominal pain.


METHODS
Rectosigmoid biopsies were collected from 23 IBS patients fulfilling Rome II criteria, and from 22 controls. Abdominal pain scores were recorded using a validated questionnaire. TRPV1-, substance P- and neuronal marker protein gene product (PGP) 9.5-expressing nerve fibres, mast cells (c-kit) and lymphocytes (CD3 and CD4) were quantified, following immunohistochemistry with specific antibodies. The biopsy findings were related to the abdominal pain scores.


RESULTS
A significant 3.5-fold increase in median numbers of TRPV1-immunoreactive fibres was found in biopsies from IBS patients compared with controls (p<0.0001). Substance P-immunoreactive fibres (p = 0.01), total nerve fibres (PGP9.5) (p = 0.002), mast cells (c-kit) (p = 0.02) and lymphocytes (CD3) (p = 0.03) were also significantly increased in the IBS group. In multivariate regression analysis, only TRPV1-immuno-reactive fibres (p = 0.005) and mast cells (p = 0.008) were significantly related to the abdominal pain score.


CONCLUSIONS
Increased TRPV1 nerve fibres are observed in IBS, together with a low-grade inflammatory response. The increased TRPV1 nerve fibres may contribute to visceral hypersensitivity and pain in IBS, and provide a novel therapeutic target.
Akbar
A
A
Department of Gastroenterology, Imperial College London, UK.
Yiangou
Y
Y
Facer
P
P
Walters
J R F
JR
Anand
P
P
Ghosh
S
S
D015746:Abdominal Pain / Q000378:metabolism* / Q000523:psychology; D000328:Adult; D000368:Aged; D001007:Anxiety / Q000378:metabolism; D003863:Depression / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000378:metabolism* / Q000523:psychology; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D050916:TRPV Cation Channels / Q000378:metabolism*
D018836:Inflammation Mediators; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human