Axonal damage in Crohn's disease is frequent, but non‐specific

Abstract

We have attempted to confirm the claim by Dvorak and Silen that 'Crohn's disease is accompanied by a severe and extensive necrosis of gut axons...[which] may serve to differentiate Crohn's disease from other inflammatory conditions'. In this electron microscope study the diagnoses were withheld until the assessment of axonal damage was completed. We assessed the axonal damage in ileostomy biopsies in 13 cases of Crohn's disease, four cases of ulcerative colitis, and two 'controls'. In Crohn's disease we found a mean per cent of abnormal axons of 29.85, in ulcerative colitis of 21.25 per cent, and in the two 'controls' of 12.11 and 10.63 per cent, respectively. The difference between the 13 cases of Crohn's disease and the six cases of non-Crohn's disease is not significant. We found considerable numbers of abnormal, very small axons of uncertain nature but probably related to regeneration following surgery. Including or excluding such axons did not significantly alter the incidence of abnormal axons. We conclude that axonal damage is common in chronic inflammatory bowel disease and is not specifically related to Crohn's disease.

Damage to the Enteric Nervous System in Experimental Colitis

“…10 The effects of inflammation on intestinal innervation in IBD are less clear, where there is controversy as to the extent, nature, and diagnostic value of such alterations. 12 There are no definitive studies of neuron number in IBD, although older reports suggest that there could be either an increase 20 or a decrease in a limited study. 21 It seems clear that there is axonal necrosis 2,22,23 as well as axonal hyperplasia.…”

“…Analysis of neurons within the submucosal plexus, lying much closer to the region of overt damage, showed a significant decrease in neuron number during colitis, from 68.3 Ϯ 4.8 12 to 41.7 Ϯ 8.7 neurons per crosssection by day 6 of inflammation. This was correlated with a significant drop in the number of ganglia, from 36.6 Ϯ 6.0 12 to 21.7 Ϯ 3.3 11 ganglia/cross section by day 6.…”

Role of neuropeptides in inflammatory bowel disease

“…27,28 Neuronal changes seen in CD include hyperplasia of the ganglion cells, extensive axonal degeneration, changes in gut neuropeptide content, and infiltration of the myenteric plexus with plasma cells, mast cells, and lymphocytes. 29,30 Patients with long-standing UC have similar but less evident alterations.…”

Origin of symptoms in diverticular disease

“…Patients with a chronic inflammatory complication of diverticular disease also demonstrate increased neural staining in the mucosa and submucosa. As nerve damage has been shown to occur in diverticulitis 102 , these findings are likely to represent a regeneration and hyperinnervation, which is a typical response of peripheral nerves following injury 100,103,104 . A similar hyperproliferation of enteric nerves and alteration in neurotransmitters has been found in the appendices of patients with chronic right iliac fossa pain and has been implicated in the pathophysiology of these symptoms 105,106 .…”