Sublingual sufentanil was developed to reduce pain following a traumatic injury in the field (e.g., battlefield). However, it is unknown whether an analgesic dose of sufentanil affects cardiovascular responses to a painful stimulus in humans. PURPOSE: We tested the hypothesis that sublingual sufentanil blunts pain perception and the accompanying cardiovascular responses during a cold pressor test (CPT). METHODS: Twenty-nine adults, 15 males and 14 females (age: 29 ± 5 years, body mass: 74 ± 8 kg, body mass index: 25 ± 2 kg/m2) participated in this double-blind, randomized, crossover, placebo-controlled trial. Following sublingual administration of sufentanil (30 µg) or placebo, participants underwent a two-minute resting baseline period and then a two-minute CPT (hand in 0.07 ± 0.10°C ice-water), while heart rate (electrocardiography) and beat-to-beat blood pressure (photoplethysmography - Finometer) were measured continuously. Pain perception (100 mm visual analog scale) was compared between trials via a two-tailed Wilcoxon Signed-Rank test. Heart rate and blood pressure responses were compared using a mixed effects model (trial x time). Changes (Δ) in heart rate and blood pressure from baseline to the last 30 seconds of the CPT were compared using a two-tailed Wilcoxon Signed-Rank test and a two-tailed paired t-test, respectively. RESULTS: Sufentanil attenuated perceived pain (sufentanil: 35 [27 – 53] vs. placebo: 68 [38 – 82] mm, p < 0.001) during the CPT. The magnitude of the increase in heart rate to the CPT was influenced by the drug (trial: p = 0.061, time: p < 0.001, interaction: p < 0.001), with the Δ heart rate being greater for the placebo trial (p = 0.002). Both absolute mean blood pressure responses (trial: p = 0.071, time: p < 0.001, interaction: p = 0.245) and Δ mean blood pressure to the CPT (sufentanil: 15 ± 9 vs. placebo: 16 ± 8, p = 0.334) were not different between trials. CONCLUSION: These data suggest that 30 µg of sublingual sufentanil attenuates perceived pain, but not the accompanying blood pressure responses, during the CPT.



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