Neuroimmune appendicitis

Background 15-25% of appendices removed from patients with suspected append icitis appear normal on histological examination. The cause of pain in such patients is unknown. Since the content of neuropeptides seems to be altere d in chronic inflammation, we investigated possible changes in peptidergic innervation for substance P (SP), vasoactive intestinal peptide (VIP), and growth-associated protein-43 (GAP-43). Methods Appendices classified as showing acute appendicitis, non-acute appe ndicitis (clinical signs of acute appendicitis, but histologically not infl amed), or normal were processed for SP, VIP, and GAP-43 immunocytochemistry . The density of SP immunostaining was assessed by digitised morphometry. Findings 31 appendix specimens were studied (16 acute, 15 non-acute). 16 sp ecimens were used as controls. Expression of GAP-43 was increased in the no n-acute appendices. We observed larger amounts of SP-immunoreactive and VIP -immunoreactive nerves in the mucosal layer of the appendix in patients wit h non-acute appendicitis than in controls and patients with acute appendici tis (mean % area SP-immunoreactive 0.0496 [SD 0.0113] non-acute, 0.0221 [0. 0049] acute, 0.0229 [0.0068] controls). In addition, a close spatial relati on between SP-immunoreactive and VIP-immunoreactive nerve fibres and lympho id cells was detected in the outer zone of lymph follicles. Interpretation Neuroproliferation in the appendix, in association with an i ncrease in neurotransmitters SP and VIP, may be involved in the pathophysio logy of acute right abdominal pain in the absence of an acute inflammation of the appendix. Our data, together with increasing knowledge about the way in which the nervous system and immune cells interact, suggest that neuroi mmune appendicitis is a distinct pathological entity.