Postoperative sensitization and pain after cesarean delivery and the effects of single IM doses of tramadol and diclofenac alone and in combination

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 μ-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 0.53; 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.