Substance P enhances neuronal area and epithelial cell proliferation after colon denervation in rats

We evaluated the neurotrophic effect of the neurokinin SP in the induced megacolon and the cell proliferation of the colonic epithelium after treatment. Colon segments of Wistar rats were chemically denervated by topical application of 2 mM benzalconium chloride and animals were daily injected intraperitoneally with SP (70 microg/kg body wt) for 15 days. Control rats received either SP or were denervated and treated with saline. Neuronal profiles of the myenteric plexus were studied by immunohistochemistry to motor protein myosin V and cell proliferation by PCNA immunolabeling. Denervation induced a significant reduction in the number of neurons and an enlargement of the surviving perikarya (from 263.7 microm2 in the control-saline group to 468.9 microm2 in the denervated groups). The total area occupied by neurons was maintained in the denarvated SP group but was significantly smaller in the denervated-saline group. The proliferative index was significantly higher in the denervated groups, of which the SP-treated group showed the highest index. These results suggest that SP may have a neurotrophic effect for the neurons of the myenteric plexus chemically denervated and that this denervation stimulates cell proliferation, especially after SP administration.