5-HT3 and histamine H-1 receptors mediate afferent nerve sensitivity to intestinal anaphylaxis in rats

Background & Aims: The mechanisms underlying brain stem activation during a ntigen challenge have not been resolved. Our aim was to characterize affere nt nerve responses to intestinal anaphylaxis and determine the mediators in volved in afferent activation. Methods: Mesenteric afferent discharge was r ecorded electrophysiologically after intestinal anaphylaxis in anesthetized rats previously sensitized to chicken egg albumin (EA), Results: Mesenteri c afferent nerve discharge increased approximately 1 minute after luminal a ntigen but not bovine serum albumin (P < 0.001, EA vs. bovine serum albumin ). Subsequent administration of antigen had no effect, but systemic EA evok ed a marked increase in afferent discharge (P < 0.05), Afferent responses w ere unrelated to intestinal motor activity, and the response to luminal ant igen was attenuated by luminal anesthetic (1% lidocaine), The 5-HT3-recepto r antagonist alosetron (30 mug.kg(-1)) and the histamine H-1-receptor antag onist pyrilamine (5 mg kg(-1)) markedly attenuated the response to luminal antigen; pretreatment with doxantrazole attenuated responses to both lumina l and systemic antigen. Conclusions: 5-HT3 and histamine, released from mas t cells after intestinal anaphylaxis, stimulate mesenteric afferents via 5- HT3 and histamine H-1 receptors, Information on intestinal immune status is rapidly relayed to the central nervous system and may play a role in neura l reflexes and behavioral responses following activation of the immune syst em.