Liver transplantation is associated with increased met-enkephalin levels in the pig

Background: It has been reported that less postoperative morphine is required following liver transplantation than is required following open cholecystectomy. This may be attributable to endogenous factors rather than to altered morphine pharmacokinetics. We measured the plasma concentrations of two endogenous neuropeptides associated with pain modulation, substance P (SP) and met-enkephalin (ME), in pigs undergoing liver transplantation and in control pigs undergoing laparotomy. Methods: With the approval of the institutional Animal Care Committee, pigs were anesthetized with ketamine (30 mg/kg, IM), atropine (0.05 mg/kg, IM) and acetylpromazine (0.1 mg/kg, IM). Anesthesia was maintained with isoflurane in oxygen. Pigs in the transplantation group (n = 10) underwent liver transplantation and control pigs (n = 10) underwent laparotomy. Blood samples for SP and ME measurement were collected pre-incision (Pre-In), pre-emergence (Pre-Em) from anesthesia, 6-12 hours, 18 hours, and 24 hours after surgery. SP and ME levels were determined by radioimmunoassay. Results are expressed as mean ± SEM (in pg/ml of plasma for both peptides) and were compared by the non-parametric Mann-Whitney U test. Statistical significance was inferred if P < 0.05. Results: Plasma ME levels were significantly increased in the transplanted pigs at Pre-Em, 6-12 hours and 18 hours after surgery. No statistically significant difference was observed for plasma SP level between the control and transplant pigs. Conclusions: Liver transplantation in the pig model is associated with increased concentrations of endogenous ME (but not SP) in plasma for at least 18 hours after surgery as compared to animals undergoing laparotomy.