Evidence for stress‐dependent mechanoreceptors linking intestinal biomechanics and sensory signal transduction

Abstract

New Findings r What is the central question of this study?Do intestinal mechanoreceptors respond primarily to stress (defined as force per unit cross sectional area) or strain (non-dimensional measure of deformation)? r What is the main finding and its importance?By using more physiological rates of filling (distension) combined with calcium channel blockade to limit active muscle tension, the adaptive properties of individual low and high threshold mechanosensitive afferents, have been examined. The slope of the stress-response relationship was not significantly different for the different populations of afferents nor for different rates of distension. These data therefore suggest that afferent activity is more closely related to stress rather than to strain. Sensory nerve endings are widely distributed throughout the body. Neither the nature of the mechanosensitive channels nor the principal mechanical stimulus for these receptors is known. Afferents supplying the gastrointestinal tract responding to distension and contraction are responsible for co-ordinated reflex control, feeding behaviour and sensations, including pain. Different populations of intestinal afferent fibres follow different pathways to the CNS, have different terminal fields and possess different thresholds for activation that may reflect the extent to which mechanical forces are distributed and dissipated by non-neural structures in the bowel wall. In this study, we have characterized the stimulus-response function of afferent fibres innervating the rat jejunum, correlating luminal distensions in the bowel wall with the firing frequency of mesenteric afferent nerve bundles. Combining video imaging with intraluminal pressure recordings and utilizing a strain softening protocol, we have determined whether mechanoreceptors respond primarily to stress or strain. Multiunit afferent recordings were separated using spike discrimination software into low-threshold (LT) and high-threshold (HT) single units. For multifibre afferent recordings and both LT and HT single units, we observed a linear relationship between circumferential stress and mesenteric afferent discharge that was independent of distension-induced tissue softening, with correlation coefficients >0.9. A fivefold change in the rate of applied distension did not significantly alter the magnitude of the afferent response and the linearity of the stress-dependent mechanotransduction in both multifibre preparations and the LT and HT afferent fibres (P > 0.2). Thus, the firing characteristics of intestinal mechanoreceptors are linearly associated with the input in terms of mechanical stress.

In vitro multichannel single-unit recordings of action potentials from the mouse sciatic nerve

“…Single-unit recordings from peripheral nerves have been mainly conducted in animals in vitro or in vivo (e.g., recordings from vagus nerves [23,24], aortic depressor nerves [25], spinal nerves [26,27], splanchnic nerves [28], and pelvic nerves [29][30][31]). To achieve a high signal-to-noise ratio, the technically challenging approach taken was to carefully isolate nerve trunks, gently splitting the trunk into fine nerve bundles, and teasing a bundle into microns-thick fine filaments.…”

Pathophysiology and treatment of achalasia in a muscle mechanical perspective

“…Furthermore, axial force is dependent on viscosity of the bolus Afferent nerve responses in the GI tract are linearly encoded with the mechanical stress stimulus . This is of huge interest for understanding symptoms in esophageal diseases characterized by disturbed mechanical function.…”

Paeoniflorin Improved Constipation in the Loperamide-Induced Rat Model via TGR5/TRPA1 Signaling-Mediated 5-Hydroxytryptamine Secretion

“…Many studies found that sensory signals in the intestinal mucosa played an important role in regulating intestinal motility, and their abnormality was closely related with STC progression [10,11].…”

“…Many studies found that sensory signals in the intestinal mucosa played an important role in regulating intestinal motility, and their abnormality was closely related with STC progression [ 10 , 11 ]. The report demonstrated that 5-hydroxytryptamine (5-HT), known as an intestinal neurotransmitter, was abnormally distributed or expressed in the colonic tissues of the STC mice model [ 12 ].…”