Session: Rising Stars of Mechanical Engineering Celebration & Showcase

Paper Number: 149676

149676 - Visceral Pain From Colon and Rectum: The Mechanotransduction and Biomechanics 

Visceral pain is a hallmark of functional gastrointestinal (GI) disorders and a primary reason for gastroenterologist visits. Visceral pain usually originates from the distal colon and rectum (colorectum), a region distinct from external body environments in terms of chemical, biological, thermal, and mechanical properties. These differences result in unique psychophysical characteristics of visceral pain compared to cutaneous pain, contributing to the limited effectiveness of conventional analgesics in treating visceral pain. Unlike cutaneous pain, which is typically induced by heat, cuts, or piercing, colorectal visceral pain is mainly triggered by mechanical distension or stretching. Thus, understanding mechanotransduction—the process by which sensory afferent nerves convert colorectal mechanical stimuli into action potentials (APs)—is crucial for elucidating GI-related visceral pain mechanisms.

This presentation will explore the mechanotransduction of the colorectal region, focusing on how mechanical stimuli are translated into AP trains that signal the central nervous system. An integrative approach has been employed, examining: 1) the neurophysiology of sensory afferents encoding colorectal mechanical stimuli, 2) the macroscopic mechanical properties of the colorectum that link physiologically relevant mechanical stimuli to local mechanical stress and strain distributions, and 3) the microscopic biomechanics around afferent nerve endings.

Through neurophysiological recordings from visceral afferents in rodent models, we have characterized the neural encoding of colorectal stimuli. Our findings indicate that 67% of colorectal afferents in the lumbar splanchnic nerve (LSN) pathway and 77% in the pelvic nerve (PN) pathway are mechanosensitive, responding to at least one of three mechanical stimuli within their receptive fields. These dominant proportions of mechanosensitive colorectal afferents are consistent with clinical observations highlighting the importance of colorectal mechanotransduction in GI-related visceral pain. Additionally, our studies show differential neural encoding characteristics between the LSN and PN innervation pathways, which predominantly innervate the proximal and distal colorectum, respectively. This neural encoding variability corresponds with the heterogeneous biomechanical properties of the colorectum, as identified through macroscopic mechanical testing. Longitudinally, compliance increases from the distal colon to the rectum, facilitating fecal storage. Through the wall thickness direction, the submucosa and muscularis propria are the primary load-bearing layers, while the mucosa and serosa exhibit negligible stiffness. Circumferentially, areas near the mesentery (mesenteric region) are more susceptible to mechanical failure than those further away (anti-mesenteric region), as suggested by the distribution of diverticular pockets in mesenteric regions observed in patients with diverticular diseases. Overall, the large intestine is stiffer longitudinally than circumferentially, reducing elongation during distension and peristalsis and helping maintain intestinal positioning.

On a microscopic scale, the intra-tissue biomechanics of the large intestine are influenced by the content, morphology, and orientation of collagen fibers in various layers. Collagen is concentrated in the submucosa and serosa but is sparse in the muscularis propria and mucosa. Submucosal collagen fibers form a helical network oriented approximately ±30° along the longitudinal axis, indicating their load-bearing role. Despite lower collagen content, the muscularis propria shows mechanical stiffness comparable to the submucosal/mucosal composite due to its thick muscle bundles in the circular and longitudinal layers. Extrinsic and intrinsic neural innervations are concentrated in the submucosa and myenteric plexus within the muscularis propria, regions subjected to high mechanical stress during distension and peristalsis. Nociceptor-like nerve endings in the submucosa likely play critical roles in detecting tissue-damaging mechanical stimuli, triggering pain from the colon and rectum.

These macro- and microscopic biomechanical features determine the local mechanical stress and strain surrounding mechanosensitive afferent endings, directly generating AP spikes. Advances in understanding colorectal biomechanics have significantly enhanced our knowledge of visceral mechanotransduction and mechano-nociception, highlighting the potential of targeting colorectal mechanotransduction as a novel approach for managing visceral pain.

Presenting Author: Bin Feng University of Connecticut

Presenting Author Biography: Dr. Feng is an Associate Professor in the Department of Biomedical Engineering at the University of Connecticut. He earned his B.S. in Precision Instruments from Tsinghua University, an M.S. in Mechanical Engineering from the University of Oklahoma, and a Ph.D. in Biomedical Engineering from Purdue University. Following this, he completed postdoctoral training in neuroscience related to visceral pain at the University of Pittsburgh. Dr. Feng now leads a multidisciplinary research team that leverages engineering techniques to advance chronic pain management. His research is supported by the National Institutes of Health (NIH), the National Science Foundation (NSF), and industry partners such as Unilever Inc. and Allergan Inc. He has published 64 peer-reviewed journal articles, 3 invention disclosures/patent publications, 5 book chapters, and 73 conference papers. Additionally, Dr. Feng co-founded CF Neuromedics, Inc., which focuses on developing improved clinical solutions for chronic pain treatment. He is a recipient of the NSF CAREER award and the Phase I Neuromod Prize.

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