Intestinal Afferent Nerve Sensitivity is Increased During the Initial Development of Postoperative Ileus in Mice

Neuronal reflex inhibition of gastrointestinal motility is a key mechanism in the development of postoperative ileus (POI). The aim of our study was to determine whether intestinal afferent nerve fibers are sensitized during the first hours after surgery contributing to this mechanism.

Under enflurane anesthesia, C57BL/6 mice underwent laparotomy followed by sham treatment or standardized small bowel manipulation to induce POI. After 1, 3, or 9 h, extracellular multi-unit mesenteric afferent nerve recordings were performed in vitro from 2 cm segments of jejunum (subgroups n = 6) superfused with Kreb’s buffer (32°C, gassed with O₂/CO₂ mixture). Segments were cannulated to monitor luminal pressure and intestinal motility. Afferent impulses as response to bradykinin (0.5 μM) and to mechanical ramp distension of the intestinal lumen from 0 to 80 cmH₂O were recorded.

At 1 h, amplitudes of intestinal contractions were 0.8 ± 0.2 cmH₂O after induction of POI and 5.0 ± 0.8 cmH₂O in sham controls (mean ± SEM; p < 0.01). A similar difference was observed for segments harvested at 3 and 9 h. Afferent firing to serosal bradykinin was increased at 1, 3, and 9 h in POI segments compared to sham controls (p < 0.05 at 1 h, p < 0.01 at 3 and 9 h). During distension with high pressures, afferent firing rate was increased at 1 and 3 h in segments after induction of POI compared to sham controls. Nine hours postoperatively, contracted and dilated segments were observed during POI that were investigated separately. While afferent firing in dilated segments was increased to 176 ± 16 imp s⁻¹ at 80 cmH₂O luminal distension (p < 0.01), it was 46 ± 5 imp s⁻¹ in contracted segments (p < 0.001) compared to 77 ± 4 imp s⁻¹ in sham controls.

Afferent firing to bradykinin and high threshold distension is augmented in the early phase of POI. As these stimuli are known to sensitize predominantly spinal afferents, this mechanism may contribute to reflex inhibition of intestinal motility during POI.