Alterations in enteric nerve and smooth‐muscle function in inflammatory bowel diseases

Although there is much focus on the factors that lead to the expression of human inflammatory bowel disease (IBD), with a view to identifying the cause(s) and cure, work is still required to better understand the pathophysiology of the disease, with views to developing innovative treatment approaches for those patients with established and often complicated disease. This review examines the nature and extent of enteric nerve and smooth‐muscle involvement in IBD. Parallels are drawn with recent animal studies, which clearly demonstrate that the deeper neuromuscular tissues of the gut are rapidly and profoundly altered after even superficial degrees of inflammation in the mucosa, and that this can occur without penetration of these tissues by the inflammatory response. In the enteric nervous system, there are quantitative and qualitative changes in neurotransmitter content, and recent work has shown that these agents (e.g., substance P) possess proin‐flammatory properties, whereas other (e.g., calcitonin gene‐related peptide) possess antiinflammatory actions. Thus, the balance of neurotransmission clearly is important in determining the expression of diseases. With respect to muscle, inflammation‐induced changes lead to alterations in contractility, which contribute to altered motility. There are also trophic changes and collagen formation that contribute to strictures of Crohn's disease. More recent work has focused on the ability of muscle to influence immune function through cytokine production, antigen presentation, and adhesion molecule expression to activate T lymphocytes. Thus, the neuromuscular tissues act not just as “innocent bystanders” but also as “active participants” in the inflamed gut.