Interdependency between mechanical parameters and afferent nerve discharge in hypertrophic intestine of rats

Abstract

Partial intestinal obstruction causes smooth muscle hypertrophy, enteric neuronal plasticity, motility disorders, and biomechanical remodeling. In this study we characterized the stimulus-response function of afferent fibers innervating the partially obstructed jejunum. A key question is whether changes in afferent firing arise from remodeled mechanical tissue properties or from adaptive afferent processes. Partial obstruction was created by placing a polyethylene ring for 2 wk in jejunum of seven rats. Sham obstruction was made in six rats and seven rats served as normal controls. Firing from mesenteric afferent nerve bundles was recorded during mechanical ramp, relaxation, and creep tests. Stress-strain, spike rate increase ratio (SRIR), and firing rate in single units were assessed for evaluation of interdependency of the mechanical stimulations, histomorphometry data, and afferent nerve discharge. Partial intestinal obstruction resulted in hypertrophy and jejunal stiffening proximal to the obstruction site. Low SRIR at low strains during fast distension and at high stresses during slow distension was found in the obstructed rats. Single unit analysis showed increased proportion of mechanosensitive units but absent high-threshold (HT) units during slow stimulation, decreased number of HT units during fast stimulation, and shift from HT sensitivity towards low threshold sensitivity in the obstructed jejunum. Biomechanical remodeling and altered afferent response to mechanical stimulations were found in the obstructed jejunum. Afferents from obstructed jejunum preserved their function in encoding ongoing mechanical stimulation but showed changes in their responsiveness. The findings support that mechanical factors rather than adaption are important for afferent remodeling.

Colonic Dysmotility in Murine Partial Colonic Obstruction Due to Functional Changes in Interstitial Cells

“…In previous reports, a partial intestinal obstruction mouse model showed ICC remodeling. 30,31 Loss of ICC could disrupt CMMC. The present data showed significant changes in the frequency of CMMC (decreased AUC) in PCO compared to controls.…”

Gastrointestinal disorders in joint hypermobility syndrome/Ehlers‐Danlos syndrome hypermobility type: A review for the gastroenterologist

“…Interestingly, investigations aimed at assessing GI motor function, such as reported by Nelson et al., have demonstrated both increased and delayed gastric emptying and colonic transit, which would suggest involvement of other mechanisms than merely alterations in the mechano‐elastic properties of the intestinal wall. Moreover, very recently, animal studies demonstrated that changes in mechano‐elastic properties of the intestine result in altered mechano‐sensory afferent responses . Indeed, considerable scientific evidence exists to support a role for the ECM in nerve function.…”

Simulations of Myenteric Neuron Dynamics in Response to Mechanical Stretch

“…The dynamic response properties of the IPANs from afferent nerve bundles to single neurons have been extensively studied [ 2 , 8 , 9 ]. Both single neurons and afferent nerve bundles exhibited similar responses in thresholds for activation and discharge rate to standard test protocols such as ramp or step distension [ 9 – 12 ]. However, many questions regarding functional aspects of the mechanical stimulus-to-mechanosensitive channels transfer characteristics of these receptors remain unknown.…”