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Inhibitory Effects of a Neurokinin‐1 Receptor Antagonist on Postoperative Peritoneal Adhesion Formation
Author(s) -
Reed Karen L.,
Stucchi Arthur F.,
Leeman Susan E.,
Becker James M.
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1418.010
Subject(s) - adhesion , medicine , proinflammatory cytokine , wound healing , receptor antagonist , antagonist , pharmacology , receptor , substance p , inflammation , immunology , neuropeptide , chemistry , organic chemistry
Intra‐abdominal adhesions are a costly, long‐term sequela of abdominal surgeries. They occur in up to 94% of patients following abdominal operation and cause significant postoperative morbidity including difficult reoperative surgeries, small bowel obstructions, and infertility. The pathophysiology of adhesion formation remains poorly defined, and a uniformly effective method of adhesion prevention does not exist. Research focused on understanding the mechanisms underlying adhesion formation is essential for the development of safe and effective therapeutic approaches to adhesion prevention. The proinflammatory peptide substance P (SP), known to participate in inflammatory and wound‐healing events, may contribute to the early processes of adhesion formation. SP is the most widely studied ligand of the neurokinin‐1 receptor (NK‐1R), and we have determined in a rat model that intraoperative administration of an NK‐1R antagonist, CJ‐12–255 (Pfizer), that blocks ligand binding to the NK‐1R, significantly reduces adhesion formation. It also has been determined that animals administered the NK‐1R antagonist intraperitoneally have increased peritoneal fibrinolytic and matrix metalloproteinase activities, and reduced levels of oxidative stress postoperatively, all of which may contribute to the observed reduction in adhesion formation. Studies suggest that intra‐abdominal adhesion formation begins within hours of surgery and that the regulation of fibrin deposition, and degradation is of key importance. A pharmacologic agent, such as an NK‐1R antagonist, administered at the time of surgery that could augment postoperative peritoneal fibrinolytic activity without compromising wound healing, would be a beneficial tool in the prevention of postoperative adhesions.