Visceral pain from colon and rectum: the mechanotransduction and biomechanics

Abstract

Visceral pain is the cardinal symptom of functional gastrointestinal (GI) disorders such as the irritable bowel syndrome (IBS) and the leading cause of patients' visit to gastroenterologists. IBS-related visceral pain usually arises from the distal colon and rectum (colorectum), an intraluminal environment that differs greatly from environment outside the body in chemical, biological, thermal, and mechanical conditions. Accordingly, visceral pain is different from cutaneous pain in several key psychophysical characteristics, which likely underlies the unsatisfactory management of visceral pain by drugs developed for other types of pain. Colorectal visceral pain is usually elicited from mechanical distension/stretch, rather than from heating, cutting, pinching, or piercing that usually evoke pain from the skin. Thus, mechanotransduction, i.e., the encoding of colorectal mechanical stimuli by sensory afferents, is crucial to the underlying mechanisms of GI-related visceral pain. This review will focus on colorectal mechanotransduction, the process of converting colorectal mechanical stimuli into trains of action potentials by the sensory afferents to inform the central nervous system (CNS). We will summarize neurophysiological studies on afferent encoding of colorectal mechanical stimuli, highlight recent advances in our understanding of colorectal biomechanics that plays critical roles in mechanotransduction, and review studies on mechano-sensitive ion channels in colorectal afferents. This review calls for focused attention on targeting colorectal mechanotransduction as a new strategy for managing visceral pain, which can also have an added benefit of limited CNS side effects, because mechanotransduction arises from peripheral organs.

Keywords: Colorectum; Irritable bowel syndrome; Mechano-sensitive ion channel; Mechanotransduction; Visceral afferents.

Conflict of interest statement

Conflict of interest: The authors claim no conflict of interests.

Figures

Figure 1.

Extrinsic afferents in the spinal innervation of mouse colon and rectum (colorectum). A) The lumbar splanchnic (LSN) and pelvic nerves (PN) dominate the innervation of the colonic and rectal regions, respectively. B) Afferent endings are differentially distributed in the colorectum between the LSN and PN innervations. Notice that proximal colonic regions out of the mesenteric zone have no spinal afferent innervations. C) Three mechanical stimuli are applied to the afferent receptive fields in the colorectum to evoke responses revealed by single-unit electrophysiological recordings. D) Colorectal afferents are categorized into 5 classes based on their response profiles to the three mechanical stimuli. Mesenteric afferents have endings not in the colorectum but in the mesentery. MPG: major pelvic ganglion; IMG: inferior mesenteric ganglion; c.stretch: circumferential stretch; HTh.prob: high-threshold probing;

Figure 2.

Mechanical heterogeneity of mouse colorectum. A) The tubular colorectum is assigned with a cylindrical coordinate system. Heterogeneous macroscale mechanical properties are reported along the axial, radial and circumferential directions. B) The collagen fibers that subserve microscale soft tissue biomechanics were measured by second-harmonic generation (SHG) microscopy through the thickness of the colorectal wall. The collagen network in the submucosa is the load-bearing structure of the colorectum. C. muscle: circular muscular layer; L. muscle: longitudinal muscular layer; submucosa (LF): submucosa under load-free condition; submucosa (ND): submucosal under noxious distension.