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Visceral Sensitivity Is Increased During the Initial Development of Postoperative Ileus in Mice
Mario H. Mueller*1, Mia Karpitschka3, Andrej Sibaev3, JöRg Glatzle2, Bing Xue1, Michael S. Kasparek1, Martin E. Kreis1
1Department of Surgery, Ludwig-Maximilians University, Munich, Germany; 2Department of Surgery, Eberhard-Karls University, Tuebingen, Germany; 3Institute of Surgical Research, Ludwig-Maximilians University, Munich, Germany
Introduction: Neurogenic, inflammatory and pharmacological alterations during surgery contribute to the pathophysiology of postoperative ileus (POI). We hypothesized that during the initial hours after surgery, afferent nerve fibers supplying the intestine are sensitized for the pain mediator bradykinin and mechanical stimuli which may contribute to efferent reflex inhibition of intestinal motility. We, therefore, aimed to explore intestinal afferent nerve sensitivity and motility during the early development of POI in mice.
Methods: Under enflurane anesthesia, C57BL/6 mice underwent laparotomy followed by sham treatment or standardized small bowel manipulation to induce ileus. Then, after 1h, 3h or 9h, extracellular multi-unit mesenteric afferent nerve recordings were established in vitro from 2 cm segments of jejunum (each subgroup n=6) continuously superfused with Krebs buffer (32°C, gassed with an O2/CO2 mixture). The segment was cannulated from both ends to monitor luminal pressure and intestinal motility simultaneously. Afferent discharge to luminal distension (0-80 cmH2O) and bradykinin (1µM) was recorded. Peak discharge frequency and intestinal motor events were analyzed by two-way ANOVA.
Results: The mean amplitude of intestinal contractions was 0.8±0.2cmH2O 1 h after induction of POI and 5±0.8 cmH2O in segments taken after 1 h from sham controls (p<0.05). A similar difference was observed for segments harvested at the 3h and 9h time point (both p<0.05). Serosal bradykinin was followed by an increase in afferent discharge to 61±6 impsec-1 after 1h, 217±25 impsec-1 after 3h and 217±6 impsec-1 after 9h in ileus segments increased compared to 46±3 impsec-1 after 1h, 57±10 impsec-1 after 3h and 140±13 impsec-1 after 9h in sham controls (*P<0.05). The afferent response during ileus was augmented at high threshold luminal distension at 80 cmH2O (912±79 impsec-1 after 1h, 933±30 impsec-1 after 3h and 1131±63 impsec-1 after 9h) when compared to sham controls (639±39 impsec-1 after 1h, 714±40 impsec-1 after 3h and 1165±30 impsec-1 after 9h), (P<0.05).
Conclusions: Afferent discharge to bradykinin and high pressure luminal distension is augmented in the early stage of postoperative ileus. As high-threshold mechanosensitivity and the algesic mediator bradykinin activate predominantly spinal afferents, spinal sensitization seems to occur at the initial stage of postoperative ileus which may trigger a reflex inhibition of intestinal motility perpetuating postoperative ileus.
