Effect of remifentanil on pain and secondary hyperalgesia associated with the heat-capsaicin sensitization model in healthy volunteers

Background: The heat-capsaicin sensitization model was developed as a nonin vasive and noninjurious human experimental pain model. The sequential appli cation of moderate intensity thermal and topical chemical stimuli produces stable and long-lasting areas of cutaneous secondary hyperalgesia. The aim of the present study was to validate the heat-capsaicin sensitization model as a tool for testing analgesic drug efficacy. Responsivity of model-assoc iated measures was tested with remifentanil, a potent and ultrashort acting mu -opioid agonist. Methods: Sensitization was induced by heating forearm skin with a thermode at 45 degreesC for 5 min, immediately followed by application of 0.075% cap saicin cream for 30 min. Sensitization was rekindled four times at 40-min i ntervals with the thermode at 40 degreesC for 5 min. After each rekindling, areas of secondary hyperalgesia were measured, and the painfulness of ther mal stimulation in normal skin with 45 degreesC for 1 min (long thermal sti mulation [LTS]) was rated. Before and during the second rekindling, remifen tanil 0.10 mug . kg(-1) . min(-1) or saline-placebo was infused for 35 min. Results: Infusion of remifentanil reduced the areas of secondary hyperalges ia to 29-30% of baseline size compared with 75-83% during placebo. Similarl y, remifentanil reduced the painfulness of LTS to 29% of baseline severity compared with 84% during placebo. Areas of secondary hyperalgesia and LTS p ainfulness returned to baseline levels by the time of the third rekindling, demonstrating rapid disappearance of remifentanil analgesia and possibly t ransient spontaneous opioid withdrawal hyperalgesia. Conclusion: Using the heat-capsaicin sensitization model, opioid analgesia and suppression of secondary hyperalgesia was reliably demonstrated without skin injury.