Neuroanatomical evidence demonstrating the existence of the vagal anti-inflammatory reflex in the intestine

Background The cholinergic anti‐inflammatory pathway is proposed to be part of the so‐called vago‐vagal ‘inflammatory reflex’. The aim of this study is to provide neuro‐anatomical evidence to support the existence of a functional neuronal circuit and its activation in response to intestinal inflammation. Methods The expression of c‐fos was evaluated at different levels of the neurocircuitry in the course of postoperative ileus (POI) in a mouse model. Specific activation of the motor neurons innervating the inflamed intestine and the spleen was monitored by retrograde tracing using cholera toxin‐b. The role of the vagal afferent pathway nerve was evaluated by selective vagal denervation of the intestine. Key Results Abdominal surgery resulted in subtle inflammation of the manipulated intestine at 24 h (late phase), but not after 2 and 6 h (early) after surgery. This local inflammation was associated with activation of neurons in the nucleus of the solitary tract and in the dorsal nucleus of the vagus. The vagal output mainly targeted the inflamed zone: 42% of motor neurons innervating the intestine expressed c‐fos IR in contrast to 7% of those innervating the spleen. Vagal denervation of the intestine abolished c‐fos expression in the brain nuclei involved in the neuronal network activated by intestinal inflammation. Conclusions & Inferences Our data demonstrate that intestinal inflammation triggers a vagally mediated circuit leading mainly to activation of vagal motor neurons connected to the inflamed intestine. These findings for the first time provide neuro‐anatomical evidence for the existence of the endogenous ‘inflammatory reflex’ and its activation during inflammation.