Tognoli E, Proto PL, Motta G, et al. - Via performing this single-center, prospective, randomized, double-blind study, researchers sought to determine the precise contribution of N-methyl-d-aspartate receptor (NMDAr) antagonism in methadone-induced analgesia. They randomly assigned 96 patients scheduled for an open laparotomy for anterior resection of the rectum to four groups: 0-Mo (placebo and morphine), K-Mo [S(+)-ketamine and morphine], 0-Me (placebo and methadone), K-Me [S(+)-ketamine and methadone]. The extent of mechanical static (punctuate) hyperalgesia to von Frey hair stimulation lateral to the surgical incision was determined as the primary end-point. The treatment group (K-Me) had peri-incisional hyperalgesia 8.4 cm (95% confidence interval, 1.5 to 15.41) lower than the control group (0-Mo) at 24 h after surgery. By modulating the hyperalgesia mechanism, acute postoperative pain was independently effectively controlled by methadone