PERIPHERAL ANALGESIC EFFECTS OF A TOPICAL FENTANYL CREAM ON A BURN INJURY IN HEALTHY VOLUNTEERS

S251 Background: Recent identification of peripheral opioid receptors [1,2] and of the potential local effectiveness of a lipid-soluble opioid administered in the periphery [3] prompted us to study the potential local benefits of topical application of a fentanyl-containing cream in an experimental burn injury. Methods: Nine healthy volunteers were asked to make magnitude estimations [4] of pain induced by a contact thermal stimulator at 1[degree sign]C increments between 43 and 52[degree sign] at four 1 x 1 cm study sites during four study phases. Each stimulus lasted 7 sec, with a 23-sec interval between stimuli. Subjects were told to assign the number zero to nonpainful sensations and a positive numerical value to each painful stimulus. The value at each site was normalized to the score at the reference site, so that the relative values assigned to different stimuli were proportional to the subject's estimate of their relative pain intensities. After baseline testing, a mild burn injury was produced at the three non-reference sites by applying the thermal stimulator at 50[degree sign]C for 100 sec; hyperalgesia was confirmed by thermal testing 20 min later. Then, either 0.01 ml of fentanyl-containing (25 [micro sign]g) or placebo cream was applied to the two most proximal sites in random double-blind fashion. Thermal testing was repeated at 1 hr and 2 hr after cream application. Repeated measures ANOVA and paired t-tests were used to compare the pain scores at different sites. Results: At 20 min after burning (before cream), testing revealed hyperal-gesia at the 3 sites which underwent burning; the increase in pain was similar at the sites destined to receive fentanyl-containing and inactive creams (p = NS). At 1 hr after cream application, the relative pain at the site treated with fentanyl cream was 26% less than that at the untreated site (p = 0.02) and 18% less than the site treated with the inactive cream (p = 0.08). At 2 hr, the fentanyl site continued to evidence lesser degrees of post-burn hyperalgesia: 22% less pain than at the untreated site (p = 0.09) and 23% less than at the site of inactive cream (p = 0.07). Figure 1 illustrates that, compared to the pain scores 20 min after burning, the improvement at the fentanyl site was significantly greater than at the placebo cream site (p<0.05).Figure 1Discussion: The data strongly indicate that topical application of a lipid-soluble opioid such as fentanyl can decrease post-injury hyperalgesia. The local administration of such an agent may prove to be a valuable component of analgesic therapy.