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BackgroundAfter surgery and loss of anesthetic effect, postoperative pain can annoy the patient and affect patient satisfaction with treatment. This study was aimed at evaluating the effect of preoperative pentoxifylline (PTX) on postoperative pain and development of secondary hyperalgesia in patients undergoing laparoscopic appendectomy (LA).MethodsThis randomized, double‐blind, placebo‐controlled clinical trial study was conducted on 91 eligible subjects with acute appendicitis referred to Shahid Beheshti hospital of Sabzevar, Iran, in 2018. The intervention and control groups were administered with a single oral dose of PTX (10 mg/kg) and placebo an hour before surgery, respectively. Postoperative pain was measured within 24 hours after surgery using a VAS, and the area of secondary hyperalgesia was measured 24 hours after surgery using the Stubhaug et al. method.ResultsThe mean age of the subjects was 26.74 ± 9.99 years, and 57.14% were female. Pain intensity during rest was significantly greater in the control group as compared to the PTX group 24 hours after surgery (VAS scores 2.19 ± 0.49 and 3.13 ± 0.66, respectively; P < 0.001). Moreover, pain intensity during cough was substantially lower in the PTX group compared with the control group 24 hours after surgery (VAS scores 2.65 ± 1.90 and 4.10 ± 2.60, respectively; P = 0.003 in turn). The dynamic hyperalgesia was significantly greater in the control group as compared with the PTX group (3.80 ± 1.82 and 7.43 ± 2.38, respectively; P < 0.001).ConclusionsFindings suggest that oral administration of PTX 1 hour before surgery in patients undergoing LA can reduce postoperative pain in patients and prevent secondary hyperalgesia at a surgical site.