Serotonin and its possible role in the painful non-inflamed appendix.

After immunohistochemical staining appendices without active inflammation but producing symptoms of appendicitis (N = 24) were compared with a control group of appendices removed incidental to another procedure (N = 26). Staining for neurone specific enolase (NSE) showed more instances of nerve 'hyperplasia' in the control group than in the appendices generating pain refuting the concept of neuroappendicopathy based on quantitative nerve changes. Serotonin staining identified subepithelial neuroendocrine cells (SNC) in 85 per cent of the specimens. All cases showed serotonin immunoreactive enterochromaffin cells (EC). Staining for serotonin was significantly decreased in the SNC in the painful group. There were no significant differences between the two groups in staining intensity of SNC and EC for substance P (SP). Vasoactive intestinal polypeptide (VIP) was not seen in the SNC and EC and there were no differences in nerve fibre staining for VIP. Serotonin is a neurotransmitter as well as mediator of inflammation. It is suggested that reduced staining for serotonin in painful appendices reflects discharge of stores which could be instrumental in inducing the pain in these cases. Continued serotonin release may then lead to acute appendicitis.