A18 STRESS TRIGGERS LOSS OF TOLERANCE TO FOOD ANTIGEN CAUSING HISTAMINE MEDIATED NEURON HYPEREXCITABILITY IN A PRECLINICAL MODEL OF IBS.

Food is a common trigger of IBS symptoms but the etiology is unclear. Increased levels of immune mediators that sensitize nerves (e.g. histamine) have been reported in IBS patients. While systemic food allergy is not a feature of IBS, it is unknown if loss of tolerance to an antigen promotes a local rather than a systemic response to the antigen. Previously we showed that short term exposure to stress and food antigen increased excitability of neurons. However, it is unknown whether stress can enable a bystander food antigen to increase neuron excitability following re-exposure to the antigen. Determine whether exposure to stress and food antigen enables release of colonic immune mediators that excite nociceptive neurons upon re-exposure to antigen. BALB/c mice were exposed to water avoidance stress (WAS) or sham stress for 1 hr daily for 10 days. On day 2–10, mice were exposed to ovalbumin (OVA) or saline (SAL). Four weeks later, mice were re-exposed to either OVA or SAL yielding 4 groups: WAS/OVA+OVA, WAS/OVA+SAL, WAS/SAL+OVA, and Sham/OVA+OVA. Mice were euthanized and a segment of colon incubated in media for 4 hrs and supernatants collected; an adjacent segment of colon was stained for mast cells by both toluidine blue and mast cell tryptase; serum was also obtained. Dorsal root ganglion (DRG) neurons from control mice were incubated with colonic supernatants and excitability was assessed by measuring rheobase (minimal current to elicit an action potential) using perforated patch clamp technique. Some DRG neurons were pre-incubated with the histamine H1 receptor antagonist pyrilamine (1 µM) 1 hr prior to supernatant addition. Mast cells numbers were assessed blindly in nonadjacent sections. Total serum IgE was measured by ELISA. Data was analyzed by one-way ANOVA with Bonferroni post test. Supernatants from WAS/OVA+OVA mice decreased the rheobase of DRG neurons compared to the WAS/OVA+SAL, WAS/SAL+OVA and Sham/OVA+OVA supernatants (75 ± 4.9 pA vs 93 ± 5.2, 94.5 ± 5.0, 94 ± 5.0 pA, respectively; p<0.05). This hyperexcitability was blocked by pyrilamine (75 ± 4.9 vs 97±5.7 pA; p<0.01). Both toluidine blue and tryptase staining showed an increase in the number of mast cells in colons from WAS/OVA+OVA compared to Sham/OVA+OVA mice (p <0.05). Total levels of IgE in the serum were not different amongst the groups. These data suggest that exposure to a bystander food antigen in presence of stress can sensitize colonic immune cells such that re-exposure to the antigen triggers release of mediators such as histamine able to sensitize nociceptive neurons. The increase in colonic mast cells suggests mast cells may be a source of these mediators. However, unaltered serum IgE suggests a local rather than a systemic sensitization. Queen’s University, Department of Medicine

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