Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome.
OBJECTIVE
Intestinal mast cell infiltration may participate to abdominal pain in irritable bowel syndrome (IBS) patients. However, the underlying mechanisms remain unknown. We assessed the effect of mast cell mediators released from the colonic mucosa of IBS patients on the activation of rat sensory neurons in vitro.


METHODS
Colonic mast cell infiltration and mediator release were assessed with quantitative immunofluorescence and immunoenzymatic assays. The effect of mucosal mediators was tested on mesenteric sensory nerve firing and Ca(2+) mobilization in dorsal root ganglia in rats.


RESULTS
Mediators from IBS patients, but not controls, markedly enhanced the firing of mesenteric nerves (14.7 +/- 3.2 imp/sec vs 2.8 +/- 1.5 imp/sec; P < .05) and stimulated mobilization of Ca(2+) in dorsal root ganglia neurons (29% +/- 4% vs 11% +/- 4%; P < .05). On average, 64% of dorsal root ganglia responsive to mediators were capsaicin-sensitive, known to mediate nociception. Histamine and tryptase were mainly localized to mucosal mast cells. IBS-dependent nerve firing and Ca(2+) mobilization were correlated with the area of the colonic lamina propria occupied by mast cells (r = 0.74; P < .01, and r = 0.78; P < .01, respectively). IBS-dependent excitation of dorsal root ganglia was inhibited by histamine H(1) receptor blockade and serine protease inactivation (inhibition of 51.7%; P < .05 and 74.5%; P < .05; respectively).


CONCLUSIONS
Mucosal mast cell mediators from IBS patients excite rat nociceptive visceral sensory nerves. These results provide new insights into the mechanism underlying visceral hypersensitivity in IBS.
Barbara
Giovanni
G
Department of Internal Medicine and Gastroenterology, and CRBA, University of Bologna, St. Orsola Hospital, Via Massarenti 9, I-40138 Bologna, Italy. gbarbara@med.unibo.it
Wang
Bingxian
B
Stanghellini
Vincenzo
V
de Giorgio
Roberto
R
Cremon
Cesare
C
Di Nardo
Giovanni
G
Trevisani
Marcello
M
Campi
Barbara
B
Geppetti
Pierangelo
P
Tonini
Marcello
M
Bunnett
Nigel W
NW
Grundy
David
D
Corinaldesi
Roberto
R
D000328:Adult; D000368:Aged; D000818:Animals; D001706:Biopsy; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D003106:Colon / Q000276:immunology / Q000294:innervation / Q000473:pathology; D017615:Enteric Nervous System / Q000166:cytology / Q000276:immunology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000276:immunology / Q000294:innervation / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D009475:Neurons, Afferent / Q000187:drug effects / Q000276:immunology; D009619:Nociceptors / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017833:Visceral Afferents / Q000276:immunology*
D018836:Inflammation Mediators; D002118:Calcium