J Oral Maxillofac Surg 70:25-30, 2012 A Double-Blind Randomized Crossover Study to Evaluate the Timing of Pregabalin for Third Molar Surgery Under Local Anesthesia Chi Wai Cheung, MBBS, FHKAM,* Wing Shan Choi, BDS, MDS,† Yiu Yan Leung, BDS, MDS,‡ Frances Lui, MBChB, FHKAM,§ Jacobus Kwok Fu Ng, MD, FHKAM, Anthony Ming Hei-Ho, MD, FHKAM,¶ and Michael Garnet Irwin, MD, FHKAM# Purpose: This double-blind randomized crossover study compared the analgesic efficacy of pre- and postoperative administration of oral pregabalin 75 mg using a postsurgical dental pain model. Materials and Methods: Patients requiring third molar surgery in 2 separate stages under local anesthesia were recruited. They were given pregabalin 75 mg either 1 hour before or after their first surgical extraction. They then received the same dose of pregabalin at their second surgical extraction, but those who received it before surgery received it postsurgery, and vice versa. Postoperative analgesic effects were assessed at postoperative hours 2, 4, 8, 12, 24, 48, and 72. Time to first analgesic, analgesic consumption and adverse events were also evaluated. Results: Forty patients were recruited, and 34 completed the study. The area under curves for numerical rating scale pain scores 1 to 24 hours were significantly lower at rest but not during mouth opening for patients receiving postoperative pregabalin (P  .048). Pain relief was similar for the period of 24 to 72 hours. No significant difference was found in time to first analgesic, total analgesic consumption, and side effects between preoperative and postoperative groups. No difference in the incidence of adverse events was noticed in relation to the timing of pregabalin administration. Conclusions: Postoperative administration of oral pregabalin 75 mg appears to offer better analgesic efficacy than preoperative administration after third molar surgery under local anesthesia. © 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:25-30, 2012 Pregabalin [(S)-(t)-3-(aminomethyl)-5-methylhexanoic acid] is an alkylated gamma-aminobutyric acid (GABA) analog pharmacologically similar to gabapentin, [1- (aminomethyl) cyclohexaneacetic acid]. It is believed to bind to the  2 -subunit of N-type voltage-gated calcium channels, 1 which reduces the release of glu- tamate, 2 thus inhibiting neuronal excitability follow- ing tissue injury. It is 3 to 10 times more potent than gabapentin. 3 Its absorption shows a linear pharmaco- kinetic profile with bioavailability exceeding 90%. 4 Its peak plasma concentration is reached within 1 hour after ingestion, and steady state is achieved within 24 *Clinical Assistant Professor, Department of Anaesthesiology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China. †Resident, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Hong Kong, Hong Kong, China. ‡Resident, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Hong Kong, Hong Kong, China. §Associate Consultant, Department of Anaesthesiology, Queen Mary Hospital, Hong Kong, China. Clinical Associate Professor, Departments of Anaesthesiology and Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China. ¶Professor, Department of Anaesthesia and Intensive Care, Chi- nese University of Hong Kong, Hong Kong, China. #Professor, Department of Anaesthesiology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China. Address correspondence and reprint requests to Dr Cheung: Department of Anaesthesiology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Room 424, Block K, Queen Mary Hospi- tal, 102 Pokfulam Rd, Hong Kong, People’s Republic of China; e-mail: cheucw@hku.hk © 2012 American Association of Oral and Maxillofacial Surgeons 0278-2391/12/7001-0$36.00/0 doi:10.1016/j.joms.2011.03.056 25