Effects of antihyperalgesic drugs on experimentally induced hyperalgesia in man.
In a double-blind, cross-over study, ibuprofen (600 mg), a peripherally-acting selective kappa-opioid receptor agonist (7.5 mg), or placebo were given orally in experiments on healthy volunteers 1 h before assessment of pain thresholds to radiant heat and of pain ratings to controlled mechanical impact stimuli. Mechanical and thermal hyperalgesia had been induced 24 h before by irradiating skin patches on the ventral side of the upper leg. UVB irradiation induced mechanical and thermal hyperalgesia at radiation dosages of three times the minimal erythema dose. UVA irradiation resulted in an immediate erythema and a delayed tanning of the skin, however, no hyperalgesia was observed. For comparison another model of mechanical hyperalgesia was applied in the same experiments which has been previously proven sensitive to non-steroidal anti-inflammatory drugs (NSAIDs). In this model hyperalgesia was assessed, which develops during repetitive pinching of skin folds (pinch model). Ibuprofen significantly diminished heat and mechanical hyperalgesia induced by UVB, but had no effect on pain responses obtained from untreated skin. It also had an antihyperalgesic effect in the pinch stimulus paradigm. In contrast, the kappa-agonist showed no antihyperalgesic efficacy in the chosen models. It is concluded that the UVB model, as the pinch model, is suitable for establishing antihyperalgesic effects of NSAIDs, but probably not of kappa-receptor agonists, in healthy human volunteers. Compared to the pinch stimulus model, the UVB model offers additional advantages: (a) drugs may be tested after induction of the skin trauma by UV and this situation is more similar to the clinical use of antihyperalgesic drugs. (b) Since mechanical and thermal hyperalgesia is induced by UVB, drug effects can be tested upon both forms of hyperalgesia.
Department of Physiology I, University of Erlangen/Nürnberg, 91054 Erlangen, Germany Merck KGaA, 64271 Darmstadt, Germany.
A
A
Bickel
S
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Dorfs
M
M
Schmelz
C
C
Forster
W
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Uhl
O H
OH
Handwerker
D000328:Adult; D000700:Analgesics / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018592:Cross-Over Studies; D004231:Diuresis / Q000187:drug effects; D004311:Double-Blind Method; D004890:Erythema / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007052:Ibuprofen / Q000627:therapeutic use*; D017078:Laser-Doppler Flowmetry; D008297:Male; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D017473:Receptors, Opioid, kappa / Q000819:agonists; D012867:Skin / Q000503:physiopathology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D017473:Receptors, Opioid, kappa; D007052:Ibuprofen