Methylprednisolone and ketorolac rapidly reduce hyperalgesia around a skin burn injury and increase pressure pain thresholds.
BACKGROUND
Glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) decrease acute postoperative pain and hyperalgesia. The objectives of this study were to investigate the effects of methylprednisolone and ketorolac on hyperalgesia around a skin burn injury and on pressure pain thresholds.


METHODS
In a double-blind, placebo-controlled, randomized trial with cross-over design, methylprednisolone 125 mg, ketorolac 60 mg or placebo was administered intravenously in 12 male volunteers on three separate days at least 4 days apart. Primary and secondary hyperalgesia were produced by a first-degree burn injury on abdominal skin 45 min before injection of the test medicines. The area of secondary mechanical hyperalgesia outside the site of injury was measured. Pressure pain stimuli were applied on the base of a fingernail, increasing until the pressure pain detection threshold (PPDT) and pressure pain tolerance threshold (PPTT) were reached.


RESULTS
Compared with placebo, the active drugs reduced the area of secondary hyperalgesia (methylprednisolone, P < 0.001; ketorolac, P < 0.01). Ketorolac but not methylprednisolone increased PPDT compared with placebo (P < 0.05). Both active drugs increased PPTT compared with placebo (methylprednisolone, P < 0.01; ketorolac, P < 0.001). Ketorolac increased PPTT more than methylprednisolone (P < 0.05).


CONCLUSIONS
Methylprednisolone and ketorolac increased PPTT attenuated secondary hyperalgesia around a skin burn injury. PPTT increased after both methylprednisolone and ketorolac. The present study demonstrates analgesic and anti-hyperalgesic properties of a glucocorticoid and a non-selective NSAID that have not been demonstrated previously in human subjects.
Stubhaug
A
A
University of Oslo, Faculty Division Rikshospitalet, Department of Anaesthesiology, Rikshospitalet Medical Centre, Oslo, Norway.
Romundstad
L
L
Kaasa
T
T
Breivik
H
H
D000328:Adult; D000698:Analgesia / Q000379:methods; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002056:Burns / Q000150:complications*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D020910:Ketorolac / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D017288:Pain Threshold / Q000187:drug effects; D011446:Prospective Studies; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005938:Glucocorticoids; D008775:Methylprednisolone; D020910:Ketorolac