title: A neurokinin 1 receptor antagonist decreases adhesion reformation after laparoscopic lysis of adhesions in a rat model of adhesion formation.
abstract: BACKGROUND
  Up to 94% of patients experience fibrous adhesions after abdominal surgery, and a significant number of these patients require a second operation for open or laparoscopic lysis of adhesions (LOA). The authors have previously shown that inhibition of the binding of tachykinin ligands to the neurokinin 1 receptor (NK-1R) using the neurokinin 1 receptor antagonist (NK-1RA) CJ-12,255 decreases primary adhesion formation and upregulates the peritoneal fibrinolytic system in a rat model. Whereas most studies have focused on the prevention of primary adhesions, few have addressed adhesion reformation after LOA. This study aimed to determine the effects of NK-1RA administration on adhesion reformation and peritoneal fibrinolytic activity after laparoscopic LOA.
  
  
  METHODS
  Adhesions were induced in 31 rats using our previously described ischemic button model. The rats underwent laparoscopy 7 days later, during which adhesions were scored and lysed followed by administration of the NK-1RA or saline. Then 7 days after LOA, 23 rats were killed and adhesions were scored. Eight rats also were killed 24 h after the LOA to obtain peritoneal tissue and fluid, which were analyzed for tissue plasminogen activator (tPA) mRNA expression and peritoneal fibrinolytic activity by reverse transcriptase-polymerase chain reaction (RT-PCR) and bioassay, respectively.
  
  
  RESULTS
  At laparoscopy, 79% +/- 3% of the buttons formed adhesions. In the saline-administered control animals, 42% +/- 3.2% of the buttons reformed adhesions after LOA (p < 0.05), whereas in the animals that received the NK-1RA, 18.2% +/- 3.5% of the buttons reformed adhesions (p < 0.05). As compared with control animals, NK-1RA administration increased tPA mRNA levels by 38% and fibrinolytic activity sixfold (p < 0.05; 7.0 +/- 2.1 U/ml vs 1.2 +/- 0.54 U/ml).
  
  
  CONCLUSIONS
  When administered during laparoscopic LOA, an NK-1RA significantly upregulates peritoneal fibrinolytic activity and decreases adhesion reformation.
authors.affiliation: Department of Surgery, Boston University School of Medicine, 88 East Newton street, C500, Boston, MA 02118, USA. scott.prushik@bmc.org
authors.forename: S G
authors.initials: SG
authors.lastname: Prushik
authors.forename: C B
authors.initials: CB
authors.lastname: Aarons
authors.forename: R
authors.initials: R
authors.lastname: Matteotti
authors.forename: K L
authors.initials: KL
authors.lastname: Reed
authors.forename: A C
authors.initials: AC
authors.lastname: Gower
authors.forename: S E
authors.initials: SE
authors.lastname: Leeman
authors.forename: A F
authors.initials: AF
authors.lastname: Stucchi
authors.forename: J M
authors.initials: JM
authors.lastname: Becker
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use*; D004195:Disease Models, Animal; D010535:Laparoscopy; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence; D000267:Tissue Adhesions / Q000517:prevention & control* / Q000601:surgery*
chemical_list: C480026:6-diphenylmethyl-5-(5-isopropyl-2-methoxybenzylamino)-1-azabicyclo(2.2.2)octane-3-carboxylic acid; D019086:Bridged Bicyclo Compounds, Heterocyclic; D064729:Neurokinin-1 Receptor Antagonists