Clinical Study Efficacy of Preoperative Administration of Paracetamol-Codeine on Pain following Impacted Mandibular Third Molar Surgery: A Randomized, Split-Mouth, Placebo-Controlled, Double-Blind Clinical Trial Maria Paola Cristalli, 1 Gerardo La Monaca, 2 Chiara De Angelis, 3 Nicola Pranno, 3 and Susanna Annibali 3 1 Department of Biotechnologies and Medical Surgical Sciences, Sapienza University of Rome, Rome, Italy 2 Department of Sense Organs, Sapienza University of Rome, Rome, Italy 3 Department of Oral and Maxillo-Facial Sciences, Sapienza University of Rome, Rome, Italy Correspondence should be addressed to Maria Paola Cristalli; mariapaola.cristalli@uniroma1.it Received 29 November 2016; Revised 11 January 2017; Accepted 17 January 2017; Published 23 February 2017 Academic Editor: Alessandro Villa Copyright © 2017 Maria Paola Cristalli et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives. Te aim of this study was to determine the efectiveness of preoperative administration of single-dose of paracetamol- codeine, in the relieving of acute postoperative pain afer the surgical removal of an impacted mandibular third molar. Materials and Methods. Te study cohort consisted of 32 Caucasian outpatients, giving a total of 64 bilateral symmetrical impacted mandibles. Patients were randomized in two experimental groups to receive a preoperative oral dose of paracetamol-codeine (analgesic group) or a placebo (placebo group) at the frst and second surgeries. Study participants were asked to record pain intensity scores during the operation and the next 2 days, the time of the frst request for rescue analgesic, and the total number of postoperative-supplement paracetamol-codeine tablets. Results. Te pain intensity score on the frst day was signifcantly lower in the analgesic group than in the placebo group ( < 0.001). Te time to using rescue therapy was signifcantly longer in the analgesic group than in the placebo group ( = 0.004). Te number of paracetamol-codeine tablets used postoperatively did not difer between the analgesic and placebo groups ( = 0.104). Conclusions. Preoperative paracetamol-codeine is efective in providing immediate postoperative pain control afer third molar surgery and in delaying the initial onset of pain. Tis trial is registered with ClinicalTrials.gov Identifer (Registration Number): NCT03049878. 1. Introduction Te removal of impacted mandibular third molars is nowa- days one of the most frequent oral surgical procedures. Nevertheless, postsurgical complications such as acute post- operative pain, swelling, bruising, and limited mouth open- ing occur frequently, and these have an immediate negative impact on the working and social lives of patients [1, 2]. Te postoperative pain is undoubtedly the most unpleasant symptom for the patient and, despite receiving analgesic therapy, may persist even 1 week afer the surgery, leading to increased morbidity and negatively infuencing the well- being and quality of life [3–5]. Various analgesic combinations have been proposed for minimizing this complication. Combining diferent phar- macologic classes of analgesic drugs that have diferent mechanisms of action and side-efect profles, resulting in additive or synergic efects, may improve the efcacy of pain therapy [6]. In addition, the use of the individual drugs at lower doses in such combinations is associated with a lower incidence of adverse efects [7, 8]. Furthermore, a single tablet containing two diferent analgesics at fxed doses seems to provide better relief of acute postoperative pain than the individual administration of the same drugs as separate tablets [9]. Tere are many reports in the literature of the efectiveness of combined Hindawi Pain Research and Management Volume 2017, Article ID 9246352, 6 pages https://doi.org/10.1155/2017/9246352