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Many lower gastrointestinal diseases are associated with altered mechanical movement and deformation of the large intestine, i.e., the colon and rectum. The leading reason for patients’ visits to gastrointestinal clinics is visceral pain, which is reliably evoked by mechanical distension rather than non-mechanical stimuli such as inflammation or heating. The macroscopic biomechanics of the large intestine were characterized by mechanical tests and the microscopic by imaging the load-bearing constituents, i.e., intestinal collagen and muscle fibers. Regions with high mechanical stresses in the large intestine (submucosa and muscularis propria) coincide with locations of submucosal and myenteric neural plexuses, indicating a functional interaction between intestinal structural biomechanics and enteric neurons. In this review, we systematically summarized experimental evidence on the macro- and micro-scale biomechanics of the colon and rectum in both health and disease. We reviewed the heterogeneous mechanical properties of the colon and rectum and surveyed the imaging methods applied to characterize collagen fibers in the intestinal wall. We also discussed the presence of extrinsic and intrinsic neural tissues within different layers of the colon and rectum. This review provides a foundation for further advancements in intestinal biomechanics by synergistically studying the interplay between tissue biomechanics and enteric neurons. [ABSTRACT FROM AUTHOR]

Mechanical distension beyond a particular threshold evokes visceral pain from distal colon and rectum (colorectum), and thus biomechanics plays a central role in visceral nociception. In this study we focused on the layered structure of the colorectum through the wall thickness and determined the biomechanical properties of layer-separated colorectal tissue. We harvested the distal 30 mm of mouse colorectum and dissected this tissue into inner and outer composite layers. The inner composite consists of the mucosa and submucosa, whereas the outer composite includes the muscular layers and serosa. We divided each composite axially into three 10-mm-long segments and conducted biaxial mechanical extension tests and opening-angle measurements for each tissue segment. In addition, we quantified the thickness of the rich collagen network in the submucosa by nonlinear imaging via second-harmonic generation (SHG). Our results reveal that the inner composite is slightly stiffer in the axial direction, whereas the outer composite is stiffer circumferentially. The stiffness of the inner composite in the axial direction is about twice that in the circumferential direction, consistent with the orientations of collagen fibers in the submucosa approximately ±30° to the axial direction. Submucosal thickness measured by SHG showed no difference from proximal to distal colorectum under the load-free condition, which likely contributes to the comparable tension stiffness of the inner composite along the colorectum. This, in turn, strongly indicates the submucosa as the load-bearing structure of the colorectum. This further implies nociceptive roles for the colorectal afferent endings in the submucosa, which likely encode tissue-injurious mechanical distension. [ABSTRACT FROM AUTHOR]

Visceral pain from the distal colon and rectum (colorectum) is a major complaint of patients with irritable bowel syndrome. Mechanotransduction of colorectal distension/stretch appears to play a critical role in visceral nociception, and further understanding requires improved knowledge of the micromechanical environments at different sub-layers of the colorectum. In this study, we conducted nonlinear imaging via second harmonic generation to quantify the thickness of each distinct through-thickness layer of the colorectum, as well as the principal orientations, corresponding dispersions in orientations, and the distributions of diameters of collagen fibers within each of these layers. From C57BL/6 mice of both sexes (8–16 weeks of age, 25–35 g), we dissected the distal 30 mm of the large bowel including the colorectum, divided these into three even segments, and harvested specimens (~8 × 8 mm2) from each segment. We stretched the specimens either by colorectal distension to 20 mmHg (reference) or 80 mmHg (deformed) or by biaxial stretch to 10 mN (reference) or 80 mN (deformed), and fixed them with 4% paraformaldehyde. We then conducted SHG imaging through the wall thickness and analyzed post-hoc using custom-built software to quantify the orientations of collagen fibers in all distinct layers. We also quantified the thickness of each layer of the colorectum, and the corresponding distributions of collagen density and diameters of fibers. We found collagen concentrated in the submucosal layer. The average diameter of collagen fibers was greatest in the submucosal layer, followed by the serosal and muscular layers. Collagen fibers aligned with muscle fibers in the two muscular layers, whereas their orientation varied greatly with location in the serosal layer. In colonic segments, thick collagen fibers in the submucosa presented two major orientations aligned approximately ±30° to the axial direction, and form a patterned network. Our results indicate the submucosa is likely the principal passive load-bearing structure of the colorectum. In addition, afferent endings in those collagen-rich regions present likely candidates of colorectal nociceptors to encode noxious distension/stretch. Image 1 • Via SHG, imaged layers within colorectums of mice: serosa, muscle, submucosa, mucosa. • Quantified layers and layer-specific collagen morphologies in colorectums of mice. • Mucosa was thickest in colonic, intermediate, rectal segments, followed by submucosa. • Submucosa had largest fiber diameters in all segments, followed by serosa and muscle. • Submucosa is thin, contains substantial collagen, and is a key load-bearing structure. [ABSTRACT FROM AUTHOR]