Aktivierung vagaler Hirnstammkerne und Sensibilität extrinsischer afferenter Nervenfasern während des postoperativen lleus bei der Maus

Abstract

Introduction: Small bowel manipulation leads to a profound ileus and an increase in spinal Fos expression, suggesting prolonged activation of spinal afferent pathways. The extent to which vagal afférents may also be influenced has not been investigated. We aimed to examine intestinal afferent sensitivity and brainstem Fos expression in mice during postoperative ileus. Methods: Under enflurane anesthesia, C57BL/6 mice underwent laparotomy followed by small bowel manipulation to induce an ileus or left untouched as a sham-treatment group. The animals were killed 24 h later. The brainstem was removed for Fos immunocytochemistry. 3 cm segments of jejunum were placed in Krebs buffer. Extracellular multiunit mesenteric afferent nerve discharge was recorded at baseline during distension and following serosal application of bradykinin (BK 1 µM). Whole nerve afferent discharge was quantified as peak increase above baseline. Fos IR was quantified in the nucleus of the solitary tract (nTS). Leukocyte infiltration into the intestinal muscularis was used an index of post-operative inflammation. Data are mean ± SEM and were compared by unpaired Students’ t-test. Results: The number of leukocytes infiltrating the muscularis was elevated during ileus (39 ± 9 vs. 1.8 ± I/mm2 in sham controls; P = 0.008). This was associated with an increase in the number of Fos-positive neurons in the nTS following surgery compared to sham controls (Bregma:- 7.70 mm, 30 ± 9 vs. 6 ± 2; P = 0.01, - 7.32 mm, 107 ± 26 vs. 6 ±2, P = 0.016, N = 4). Spontaneous discharge was higher in ileus animals compared to sham segments (17 ± 1 vs. 12 ± 2 imp/s, P = 0.02, N = 6), but not in the peak response to ramp distension (at 60 mmHg 85 ± 6 vs. 70 ± 4 imp/s respectively, P = 0.07). The response profile was different in ileus with a significantly increased response at low distending pressures (2 -20 mmHg) compared to controls (18 ±2 imp/s vs 9 ±2, P < 0.05). The level of firing after BK adminstration was not significantly different during ileus (58 db 8 imp/s vs 39 db 9 imp/s, N = 8, n.s.). Conclusion: Small bowel manipulation leads to a markely increase in brainstem Fos expression indicating that vagal afferent pathways are activated during postoperative ileus. Mechanical manipulation leads to an augmented afferent sensitivity to low distending pressures. The increased sensitivity to low threshold distension might be due to local inflammatory processes. This activation is not reflected by changes in afferent sensitivity due to chemical stimulation, suggesting there may be compensatory changes to limit inflammation-induced hypersensitivity.