Visceral pain from colon and rectum: the mechanotransduction and biomechanics

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.