title: Postoperative sensitization and pain after cesarean delivery and the effects of single im doses of tramadol and diclofenac alone and in combination.
abstract: Combining different analgesic mechanisms can reduce postoperative pain. We investigated postoperative pain and sensory sensitization in a double-blinded, placebo-controlled, randomized, single-dose comparison of the monoaminergic and micro -opioid agonist tramadol, 100 mg, and diclofenac 75 mg given IM in combination or alone in 120 patients who had elective cesarean delivery. The time to first postoperative demand for rescue analgesia, pain, tramadol pharmacokinetics, and electrical sensory thresholds at or distant from the incision were studied. The median time to first rescue (interquartile range) was 197 min (70-1000 min) with tramadol plus diclofenac, 48 min (25-90 min) with tramadol plus placebo, 113 min (35-270 min) with diclofenac plus placebo, and 55 min (30-100 min) with double placebo (tramadol plus diclofenac versus all other groups, P < 0.05). Pain intensity decreased markedly over time in all groups, and time and drug effects were significant (analysis of variance; P < 0.00001). Side effects were similarly minimal with all treatments. Pain thresholds at or distant from the incision increased significantly after surgery only with tramadol plus diclofenac. Preoperative sensory thresholds correlated with postoperative sensory changes (r > 0.53; P < 0.0001). The pharmacokinetics of tramadol and O-desmethyltramadol were unchanged by diclofenac. The combination of tramadol and diclofenac resulted in improved analgesia compared with monotherapy. Only the analgesic combination prevented both primary and secondary hyperalgesia. Preoperative sensory thresholds may allow prediction of postoperative sensitization.
  
  
  CONCLUSIONS
  The parenteral combination of tramadol and diclofenac resulted in more prolonged and pronounced postoperative analgesia and reduced sensory sensitization compared with the single drugs, with no increase in side effects.
authors.affiliation: *Visceral Physiology Institute and Departments of †Anaesthetics and ‡Obstetrics and Gynaecology, Groote Schuur Hospital, University of Cape Town, South Africa.
authors.forename: Clive H
authors.initials: CH
authors.lastname: Wilder-Smith
authors.forename: Lauren
authors.initials: L
authors.lastname: Hill
authors.forename: Robert A
authors.initials: RA
authors.lastname: Dyer
authors.forename: Gregory
authors.initials: G
authors.lastname: Torr
authors.forename: Ed
authors.initials: E
authors.lastname: Coetzee
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002585:Cesarean Section; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008875:Middle Aged; D010147:Pain Measurement; D017288:Pain Threshold; D010149:Postoperative Pain / Q000188:drug therapy / Q000517:prevention & control*; D020250:Postoperative Nausea and Vomiting / Q000139:chemically induced; D011247:Pregnancy; D011446:Prospective Studies; D014147:Tramadol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D014147:Tramadol