Cumulative VAS scores (0–100).

<p>VAS/minute and standard deviation reported by the volunteers during the burn injury (Day 1+3) and BTS (Day 1+2+3+4). No difference in cumulative VAS was observed between Day 1 and 3 during the burn injury (<i>P = </i>0.21) and during BTS (<i>P = </i>0.09). There was a significant difference between Day 1 and 2 (<i>P</i><0.01), and Day 3 and 4 in VAS ratings during BTS (P<0.05). BTS = Brief thermal stimulation.</p

Demographic data.

<p>Mean values±SD.</p

Detailed timetable algorithm of the study.

<p>(Study Days 1 and 2, and, Study Days 3 and 4 are identical). BL = baseline (warmth detection thresholds, heat pain thresholds, pinprick pain thresholds, secondary hyperalgesia areas in brief thermal stimulation and burn injury sites), Nx-INF = Naloxone target-controlled infusion (see text for detailed explanation). 1/2/3 PB = postburn assessments 1, 2 and 3 hrs after the burn injury (secondary hyperalgesia areas on brief thermal stimulation and burn injury sites), 72 PB = postburn assessments 72 hrs after the burn injury (pinprick pain thresholds, secondary hyperalgesia areas on brief thermal stimulation and burn injury sites), 73 PB = postburn assessments 73 hrs after the burn injury (warmth detection thresholds, heat pain thresholds, pinprick pain thresholds, secondary hyperalgesia areas on brief thermal stimulation and burn injury sites).</p

Study algorithm.

<p>The study was performed on 5 separate days. Day 0 corresponded to the screening day; Day 1 and Day 3 were the burn injury days separated by 72 hrs from the drug administration days, Day 2 and Day 4.</p

WDT, WDT and PPT.

<p>Mean value and standard deviation of WDT and HPT are shown in this table, as well as median values and 25–75% IQR of PPT. On Day 2 and 4, pin-prick assessments were performed before and after i.v. administration of naloxone or placebo, whereas HPT and WDT were only assessed after drug infusion. Naloxone administration was not associated with changes in WDT (<i>P = </i>0.39), HPT (<i>P = </i>0.21) and PPT (<i>P = </i>0.98). There were no significant differences in WDT and HPT, assessed in the BI-area, between Day 1 and 2 ([baseline <i>vs.</i> 73 hrs PB, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064608#pone-0064608-g002" target="_blank">Fig. 2</a>] <i>P = </i>0.10, <i>P = </i>0.27, respectively), and between Day 3 and 4 (<i>P = </i>0.13, <i>P = </i>0.12, respectively).</p><p>HPT = Heat pain thresholds, PPT = Pin-prick thresholds, WDT = Warmth detection thresholds.</p

Size of secondary hyperalgesia areas after naloxone or placebo administration.

<p>Individual secondary hyperalgesia areas (▵-values = post-infusion area – pre-infusion area) at burn injury site in cm² after administration of naloxone and placebo, 72 hrs post-burn. The median (25–75% interquartile range) change in secondary hyperalgesia areas after naloxone administration was 1.87 cm² (0.74–7.00) and after placebo administration 3.10 cm² (1.48–11.42). Magnitude of secondary hyperalgesia areas was not associated with naloxone-treated compared to placebo-treated subjects (<i>P = </i>0.25).</p

Inclusion and exclusion criteria.

<p>Inclusion and exclusion criteria.</p