Interplay between mast cells, enterochromaffin cells, and sensory signaling in the aging human bowel

BACKGROUND: Advanced age is associated with a reduction in clinical visceral pain perception. However, the underlying mechanisms remain largely unknown. Previous studies have suggested that an abnormal interplay between mast cells, enterochromaffin (EC) cells, and afferent nerves contribute to nociception in gastrointestinal disorders. The aim of this study was to investigate how aging affects afferent sensitivity and neuro‐immune association in the human bowel. METHODS: Mechanical and chemical sensitivity of human bowel afferents were examined by ex vivo afferent nerve recordings. Age‐related changes in the density of mast cells, EC cells, sensory nerve terminals, and mast cell‐nerve micro‐anatomical association were investigated by histological and immune staining. KEY RESULTS: Human afferents could be broadly classified into subpopulations displaying mechanical and chemical sensitivity, adaptation, chemo‐sensitization, and recruitment. Interestingly human bowel afferent nerve sensitivity was attenuated with age. The density of substance P‐immunoreactive (SP‐IR) nerve varicosities was also reduced with age. In contrast, the density of ileal and colonic mucosal mast cells was increased with age, as was ileal EC cell number. An increased proportion of mast cells was found in close apposition to SP‐IR nerves. CONCLUSIONS & INFERENCES: Afferent sensitivity in human bowel was reduced with advancing age. Augmentation of mast cells and EC cell numbers and the mast cell‐nerve association suggest a compensatory mechanism for sensory neurodegeneration.