Regenerating vagal afferents reinnervate gastrointestinal tract smooth muscle of the rat.

Peripheral projections of the vagus are known to regenerate after subdiaphragmatic vagotomy, but neither the question of whether the regenerating axons are motor or sensory nor the issue of whether the fibers reinnervate their original targets have been addressed. To determine whether vagal afferents regenerate and whether they differentiate into normal terminal specializations in the reinnervated target organ, male Sprague-Dawley rats underwent complete subdiaphragmatic vagotomies and were injected 18 weeks later with 3 microl of 4% wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in the left nodose ganglion. To provide a comparison group, an unoperated group (controls) was injected with WGA-HRP in the left nodose ganglion. The esophagus, the entire stomach, the first 8 cm of the duodenum, and the hilus of the liver were prepared as wholemounts and processed with tetramethyl benzidine. Vagal afferents were found to have regenerated and reinnervated the esophagus, stomach, duodenum, and liver. Bundles (two or more axons), individual vagal axons, and terminals in the stomach were counted and mapped with a sampling grid. At 18 weeks postvagotomy, the reinnervated stomach and duodenum contained normal terminals as well as aberrant endings and growth cone profiles. The ingrowing axons reestablished ipsilateral and contralateral projections in the same proportions seen in controls, although the overall density of the different regenerating elements had reached only 7-39% of control values. These findings demonstrate that the gastrointestinal tract and liver can undergo dramatic afferent reinnervation after vagotomy. The presence of differentiated endings at 18 weeks suggests that some afferent function(s) may be restored, and the expression of growth cones suggests that additional regeneration may be ongoing. Copyright 2000 Wiley-Liss, Inc.