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PAIN MEDICINE

The Effects of Remifentanil and Gabapentin on Hyperalgesia in a New Extended Inflammatory Skin Pain Model in Healthy Volunteers

From the Department of Anesthesia and General Intensive Care Medicine (B), University of Vienna, Vienna, Austria

Address correspondence and request for reprints to: Burkhard Gustorff, MD, DEAA, Department of Anesthesia and General Intensive Care Medicine (B), University of Vienna, Währinger-Gürtel 18–20, A-1090 Vienna, Austria. Address email to burkhard.gustorff{at}univie.ac.at

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 µg · 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°C; 95% confidence interval [CI], 3.32°–5.59°) and heat pain tolerance thresholds (HPTT; mean difference, 5.43°C; 95% CI, 4.50°–6.35°) 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°C; 95% CI, 1.86°–3.09°, P < 0.001) and HPTT (mean increase, 3.18°C; 95% CI, 2.65°–3.71°, P < 0.001) and reduced the area of secondary hyperalgesia by 59% (mean decrease, 5326 mm²; 95% CI, 4233–6419 mm², P < 0.001) compared with placebo. In the sunburn remifentanil markedly increased the HPTT by 86% compared with normal skin (additional increase, 2.57°C; 95% CI, 1.71°–3.43°). 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.

IMPLICATIONS: 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.

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