Analgesic effect of melatonin in children undergoing surgery: a pilot randomized, placebo-controlled study

Background: Pediatric patients undergoing surgery may experience significant postoperative pain. Long-term consequences of pain are detrimental. We tested the hypothesis that melatonin (Mel) reduces postoperative pain in children undergoing surgery Methods: This study was conducted as a randomized clinical trial in a single university children's hospital (September 2022 to March 2023). Thirty-two patients (mean age: 5 years) undergoing elective pediatric surgery were enrolled and randomly divided into a group receiving 5 mg of melatonin (Mel-group) and a group receiving a placebo (Control group). The primary outcome was evaluation of 4-hydroxynonenal (4-HNE) at T0 before hospitalization, 1 hour before surgery (T1), and 1 hour after surgery (T2). Secondary outcome was occurrence of pain up to 48 hours after surgery included. Plasma melatonin levels were also monitored. Data were analyzed using GraphPad Prism 6.0. Results: Melatonin concentrations increased significantly from T0 to T2 in melatonin-treated infants, with a significant positive correlation between T1 and T2 melatonin concentrations. 4-HNE plasma levels increased significantly from T0 to T2 in all babies. The treated group showed significantly lower 4-HNE concentration than the control group at T2 (14.0 ± 0.97 ng/mL vs 15.9 ± 1.93 ng/mL). A statistically significant correlations were found between melatonin and 4-HNE (r=-0.42; p= 0.02), and between 4-HNE and pain score, during the recovery period (r=0.44; p=0.03), (Figures 1 and 2) Conclusions: The analgesic effect of melatonin administration in children undergoing surgery is associated with a reduction in perioperative OS. The data suggest a potential benefit of melatonin for pain and distress in children undergoing medical procedures and thus provide a precursor for further studies investigating the efficacy of melatonin.