The effects of remifentanil and gabapentin on hyperalgesia in a new extended inflammatory skin pain model in healthy volunteers.
We tested the responsiveness of measures of hyperalgesia in a model of UVB-induced inflammatory hyperalgesia with remifentanil, gabapentin, and the combination of both drugs in a double-blinded, active placebo-controlled, 4-way-crossover design in 16 volunteers. A circular skin area was irradiated with UVB-light 20 h before the application of gabapentin (600 mg) and 2 h later remifentanil (0.08 microg.kg(-1).min(-1), 40 min). In the sunburn spots we observed stable decreases of the heat pain perception thresholds (HPPT, mean difference, 4.45 degrees C; 95% confidence interval [CI], 3.32 degrees -5.59 degrees ) and heat pain tolerance thresholds (HPTT; mean difference, 5.43 degrees C; 95% CI, 4.50 degrees -6.35 degrees ) compared with normal skin. Further, large areas of mechanical hyperalgesia to pinprick adjacent to the erythema spots developed in all subjects. Overall remifentanil increased the HPPT (mean increase, 2.47 degrees C; 95% CI, 1.86 degrees -3.09 degrees, P < 0.001) and HPTT (mean increase, 3.18 degrees C; 95% CI, 2.65 degrees -3.71 degrees, P < 0.001) and reduced the area of secondary hyperalgesia by 59% (mean decrease, 5326 mm(2); 95% CI, 4233-6419 mm(2), P < 0.001) compared with placebo. In the sunburn remifentanil markedly increased the HPTT by 86% compared with normal skin (additional increase, 2.57 degrees C; 95% CI, 1.71 degrees -3.43 degrees). This different effect was not seen in the HPPT. With the exception of a small increase of HPTT in the sunburn (P = 0.02) gabapentin had no noticeable effect on either hyperalgesia. In conclusion, opioid analgesia was reliably demonstrated in this new extended pain model.


CONCLUSIONS
Opioid analgesia was reliably demonstrated in a new inflammatory model of primary and secondary hyperalgesia. Gabapentin showed no antihyperalgesic and no opioid-enhancing effect in this model.
Gustorff
Burkhard
B
From the Department of Anesthesia and General Intensive Care Medicine (B), University of Vienna, Vienna, Austria.
Hoechtl
Katharina
K
Sycha
Thomas
T
Felouzis
Evangelos
E
Lehr
Stephan
S
Kress
Hans G
HG
D000085:Acetates / Q000627:therapeutic use*; D000328:Adult; D000588:Amines; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003509:Cyclohexanecarboxylic Acids; D003975:Diazepam / Q000494:pharmacology; D004311:Double-Blind Method; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology; D000077206:Gabapentin; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000473:pathology; D007249:Inflammation / Q000150:complications* / Q000473:pathology; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D010880:Piperidines / Q000627:therapeutic use*; D011930:Reaction Time / Q000187:drug effects; D000077208:Remifentanil; D012867:Skin / Q000473:pathology*; D013471:Sunburn / Q000150:complications / Q000473:pathology; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000701:Analgesics, Opioid; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D010880:Piperidines; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000077208:Remifentanil; D003975:Diazepam