Predicting the micromechanics of embedded nerve fibers using a novel three-layered model of mouse distal colon and rectum

Abstract

Mechanotransduction plays a central role in evoking pain from the distal colon and rectum (colorectum) where embedded sensory nerve endings convert micromechanical stresses and strains into neural action potentials. The colorectum displays strong through-thickness and longitudinal heterogeneity with collagen concentrated in the submucosa thus indicating the significant load-bearing role of this layer. The density of sensory nerve endings is also significantly the greatest in the submucosa, suggesting a nociceptive function. Thus biomechanical heterogeneity in the colorectum influences the micromechanical stresses and strains surrounding afferent endings embedded within different layers of the colorectum which is critical for the mechanotransduction of various mechanical stimuli. In this study we aimed to: (1) calibrate and validate a three-layered computational model of the colorectum; (2) predict intra-tissue distributions of stresses and strains during mechanical stimulation of the colorectum ex vivo (i.e. circumferential stretching, punctuate probing, and mucosal shearing); and (3) establish a methodology to calculate local micromechanical stresses and strains surrounding afferent nerve endings embedded in the colorectum. We established three-layered FE models that include mucosa, submucosa, and muscular layers, and incorporated residual stretches, to calculate intra-tissue stresses and strains when the colorectum undergoes the mechanical stimuli used to characterize afferent neural encoding ex vivo. Finally, we established a methodology for detailed calculations of the local micromechanical stresses and strains surrounding afferent endings embedded in the colorectum and demonstrated this with a representative example. Our novel methodologies will bridge the existing neurophysiological and biomechanical evidence from experiments to advance our mechanistic understanding of colorectal mechanotransduction.