Systemic capsaicin inhibits neuronal activation in the brainstem during postoperative ileus in the mouse

Abstract

Neuronal inhibitory reflex mechanisms contribute to postoperative ileus after abdominal surgery. During this condition, sensory neurons in the brainstem are activated. We aimed to determine the contribution of capsaicin-sensitive afferents to central vagal sensitivity in mice during postoperative ileus. Under enflurane anesthesia, C57BL/6 mice were laparotomized and the small bowel was manipulated to induce ileus or was left untouched as a sham-treatment group. A subgroup of ileus animals was pre-treated with Capsaicin (1 microm/kg, i.p.) 48 h before small bowel manipulation. The animals were killed 24 h later and the brainstem was removed for Fos immunohistochemistry, which was quantified in the nucleus of the solitary tract (nTS). Spontaneous jejunal motility was recorded in vitro. Leukocyte infiltration in the intestinal muscularis was studied by myeloperoxidase staining as an index of postoperative inflammation. There were 30+/-9 Fos-positive neurons counted in the nTS after ileus and 6+/-2 in sham controls (Bregma -7.70 mm, P=0.01). A reduction to 8+/-3 was observed after Capsaicin pre-treatment in ileus animals (P<0.05). Peak amplitudes of spontaneous jejunal motility were 2+/-0.3 cmH2O during postoperative ileus, 3+/-0.6 cmH2O after ileus with capsaicin pre-treatment, and 10+/-2 cmH2O in control animals (N=6, both P<0.05). The number of leukocytes infiltrating the muscularis was 39+/-9/mm2 during ileus and 1.8+/-1/mm2 in controls (mean+/-SEM, P<0.01, N=6). After capsaicin, this number increased to 72+/-28/mm2 in ileus animals (P<0.05 vs control animals, N=7). The inhibition of capsaicin-sensitive vagal afferent pathways appears to boost rather than to attenuate the inflammatory response during postoperative ileus, while intestinal motility remained unchanged. This suggests a protective role of the capsaicin-sensitive afferent innervation for the inflammatory phase of postoperative ileus.