NF-kappaB activation precedes increases in mRNA encoding neurokinin-1 receptor, proinflammatory cytokines, and adhesion molecules in dextran sulfate sodium-induced colitis in rats.

Nuclear factor kappa B (NF-kappa B) plays a key role in initiating inflammation associated with colitis. A systematic study was conducted in the rat DSS colitis model to determine the temporal relationship between NF-kappa B activation and expression of substance P (SP), neurokinin-1 receptor (NK-1R), proinflammatory cytokines, and adhesion molecules. Rats were given 5% DSS in their water and sacrificed daily for 6 days.

A neurokinin 1 receptor antagonist decreases postoperative peritoneal adhesion formation and increases peritoneal fibrinolytic activity.

Fibrous adhesions remain a major sequela of abdominal surgery. The proinflammatory peptide substance P (SP), known to participate in inflammatory events, may play a key role in adhesion formation. This hypothesis was tested by using an antagonist, CJ-12,255 (Pfizer), that blocks the binding of SP to the neurokinin 1 receptor (NK-1R).

A neurokinin 1 receptor antagonist reduces an ongoing ileal pouch inflammation and the response to a subsequent inflammatory stimulus.

Ileal pouch-anal anastomosis (IPAA) is an excellent surgical option for patients with chronic ulcerative colitis (CUC) requiring colectomy; however, persistent episodes of ileal pouch inflammation, or pouchitis, may result in debilitating postoperative complications. Because considerable evidence implicates substance P (SP) as an inflammatory mediator of CUC, we investigated whether SP participates in the pathophysiology of pouchitis. With the use of a rat model of IPAA that we developed, we showed that ileal pouch MPO levels and neurokinin 1 receptor (NK-1R) protein expression by Western blot analysis were significantly elevated 28 days after IPAA surgery.

Colonic metaplasia in the ileal pouch is associated with inflammation and is not the result of long-term adaptation.

Ileal pouch-anal anastomosis (IPAA) is the preferred surgical therapy for chronic ulcerative colitis (CUC) and familial adenomatous polyposis (FAP). Previous studies have demonstrated morphologic changes in pouch mucosa such as villous atrophy and crypt hyperplasia. These changes have been labeled "colonic metaplasia.

Neurokinin-1 receptor and substance P messenger RNA levels increase during intraabdominal adhesion formation.

Background: Intraabdominal peritoneal adhesions are a significant cause of postoperative morbidity and remain one of the major long-term complications associated with abdominal surgery. Adhesion formation at the molecular level involves a complex interaction of cytokines, growth factors, cell adhesion molecules, and neuropeptides, as well as many other factors secreted by cells proximate to the traumatized area. Limited studies exist which investigate the molecular processes involved in adhesion formation.

Pouchitis in a rat model of ileal J pouch-anal anastomosis.

Endorectal ileal pouch-anal anastomosis (IPAA) has become the operation of choice for patients with chronic ulcerative colitis. Although this procedure improves the quality of life, pouchitis remains a significant postoperative complication. Because our understanding of the pathophysiology of pouchitis may, in part, be due to the lack of small animal model, our aim was to develop a model of IPAA in a rat that mimics its clinical counterpart.