Effects of Glucocorticoids and Nonsteroidal Anti-inflammatory Drugs on Postoperative and Experimental Pain

Optimizing non-opioid pain relief postoperatively is necessary to spare opioids, reduce opioid related side effects, increase the quality of analgesia, facilitate postoperative recovery and hopefully prevent chronic postoperative pain. In the present thesis, Luis Romundstad and co-workers investigated the effect of adding paracetamol (propacetamol 2 g i.v.) to an NSAID (ketorolac 30 mg i.v.) on human experimental pain, and the effect of a glucocorticoid (methylprednisolone 125 mg i.v.) on hyperalgesia, rescue analgesic use, postoperative emesis and fatigue in human postoperative and experimental pain models. They compared methylprednisolone with placebo, an NSAID (ketorolac 30 mg and 60 mg i.v.), or a selective COX-2 inhibitor (parecoxib 40 mg i.v.). They also studied the prevalence of chronic postoperative pain and sensory changes and the effect of methylprednisolone and parecoxib on these variables. For the first time a glucocorticoid (methylprednisolone), and an NSAID (ketorolac), was shown to decrease secondary hyperalgesia, indicating a central anti-hyperalgesic effect of these drugs. Methylprednisolone and ketorolac increased the tolerance threshold for painful pressure, and adding paracetamol to ketorolac increased this tolerance further compared with ketorolac alone. Methylprednisolone and the active comparators ketorolac and parecoxib reduced acute postoperative pain. Methylprednisolone also reduced postoperative emesis, fatigue and persistent postoperative hyperesthesia. This thesis adds to the pool of evidence documenting that chronic postoperative pain and sensory changes are relatively common, with a 13% prevalence of pain and 46% hyperesthesia one year after breast augmentation surgery. According to the results in the present thesis we advocate the combination of NSAIDs and paracetamol, and/or a single, appropriate perioperative dose of a glucocorticoid in order to optimize postoperative pain relief