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Introduction: Postoperative adhesions occur in 90-100% of patients after abdominopelvic surgery. We previously showed that adhesiogenesis is associated with leukocyte migration into the peritoneum and that the NK1R plays an important role in adhesiogenesis. The aim of this study was to characterize the temporal changes and the effects of a NK-1RA on the gene expression of the leukocyte chemoattractants CXCL1 and CXCL2 during adhesiogenesis.
Methods: Adhesions were induced in mice using our previously published cecal cauterization model. Wild-type (WT) mice (n =7/group) were administered saline (WT+S) or a NK-1RA (WT+NK) (25mg/kg) intraperitoneally at surgery. At 0, 3, and 6-hrs post-operatively, cecal adhesion tissue was measured for CXCL1, CXCL2 and CXCR2 mRNA levels by real-time-PCR. Adhesions were measured on POD 7 (n=7/group) in WT, WT+NK and CXCR2 knockout (KO) mice.
RESULTS: In WT+S mice, CXCL1 and CXCL2 mRNA levels increased at 3-hrs post-operatively compared to non-operated controls (380.8±143 vs 0.04±0.08; p<0.05; 198.3±105 vs 0.07±0.05; p<0.05) while CXCR2 mRNA increased at 6-hrs (16.5±2.9 vs 0.17±0.06; p<0.05). Administration of the NK-1RA significantly reduced mRNA levels of CXCL1 and CXCL2 3hrs post-operatively compared to controls (380.8±143 vs 89.9±23.7; p<0.05; 198.3±105 vs 22.7±6.2; p<0.05) while CXCR2 mRNA levels were reduced by 64% (16.5±2.8 vs 5.9±1.6; p<0.05) at 6hrs. Adhesion formation was reduced in both WT+NK and CXCR2 KO mice by 55% (4.8±0.16 vs 2.2±0.19; p<0.05) and 56% (5.0±0.0 vs 2.2±0.2; p<0.05), respectively compared to WT+S.
CONCLUSIONS: These data suggest that the NK-1R mediates leukocyte migration into the peritoneum indicating a new role for the NK-1RA in adhesiogenesis.