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Dezocine is proposed as an adjunctive analgesic for postoperative pain control. This randomized, double-blind, controlled study aimed to investigate the effect of preoperative Dezocine therapy on postoperative pain following laparoscopic cholecystectomy as well as the underlying mechanisms.Eighty patients scheduled for laparoscopic cholecystectomy were randomly allocated into 2 groups as follows: patients in Group D received Dezocine 0.15 mg/kg before anesthesia induction and patients in Group S received same volume of saline. The pain intensity, sedation score, sufentanil-based patient-controlled analgesia (PCA) consumption were recorded for 24 hours after surgery. Plasma concentrations of norepinephrine and serotonin were also measured.During the first 24 hours after surgery, the patients in Group D experienced lower pain score assessed by numerical rating scale (NRS) at 3 hours (rest: P = .038; movement: P = .036), 6 hours (rest: P = .038; movement: P = .036), 12 hours (rest: P = .038; movement: P = .036), and 24 hours (rest: P = .038; movement: P = .036). Dezocine also decreased the sedation levels at 5 minutes (P = .031) after arrival at the PACU. Sufentanil-based PCA consumption in Group D was decreased when compared with Group S in the second to fourth phase after surgery (6–12 hours: P = .017; 12–18 hours: P = .003; 18–24 hours: P = .039). Plasma norepinephrine and serotonin concentrations were higher in the Group D at 24 hours after surgery (norepinephrine: P = .009, serotonin: P = .042). In addition, Group D showed less incidence of nausea/vomiting (P = .032) as well as a higher postoperative satisfaction score after surgery (P = .017).In conclusion, preemptive Dezocine administration is suggested to be useful for the management of postoperative pain in short-lasting surgery such as laparoscopic cholecystectomy.