High-dose naloxone: Effects by late administration on pain and hyperalgesia following a human heat injury model. A randomized, double-blind, placebo-controlled, crossover trial with an enriched enrollment design

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

High-dose naloxone : Effects by late administration on pain and hyperalgesia following a human heat injury model. A randomized, double-blind, placebo-controlled, crossover trial with an enriched enrollment design. / Springborg, Anders Deichmann; Jensen, Elisabeth Kjær; Kreilgaard, Mads; Petersen, Morten Aagaard; Papathanasiou, Theodoros; Lund, Trine Meldgaard; Taylor, Bradley Kenneth; Werner, Mads Utke.

In: PLoS ONE, Vol. 15, No. 11, e0242169, 2020.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Springborg, AD, Jensen, EK, Kreilgaard, M, Petersen, MA, Papathanasiou, T, Lund, TM, Taylor, BK & Werner, MU 2020, 'High-dose naloxone: Effects by late administration on pain and hyperalgesia following a human heat injury model. A randomized, double-blind, placebo-controlled, crossover trial with an enriched enrollment design', PLoS ONE, vol. 15, no. 11, e0242169. https://doi.org/10.1371/journal.pone.0242169

APA

Springborg, A. D., Jensen, E. K., Kreilgaard, M., Petersen, M. A., Papathanasiou, T., Lund, T. M., Taylor, B. K., & Werner, M. U. (2020). High-dose naloxone: Effects by late administration on pain and hyperalgesia following a human heat injury model. A randomized, double-blind, placebo-controlled, crossover trial with an enriched enrollment design. PLoS ONE, 15(11), [e0242169]. https://doi.org/10.1371/journal.pone.0242169

Vancouver

Springborg AD, Jensen EK, Kreilgaard M, Petersen MA, Papathanasiou T, Lund TM et al. High-dose naloxone: Effects by late administration on pain and hyperalgesia following a human heat injury model. A randomized, double-blind, placebo-controlled, crossover trial with an enriched enrollment design. PLoS ONE. 2020;15(11). e0242169. https://doi.org/10.1371/journal.pone.0242169

Author

Springborg, Anders Deichmann ; Jensen, Elisabeth Kjær ; Kreilgaard, Mads ; Petersen, Morten Aagaard ; Papathanasiou, Theodoros ; Lund, Trine Meldgaard ; Taylor, Bradley Kenneth ; Werner, Mads Utke. / High-dose naloxone : Effects by late administration on pain and hyperalgesia following a human heat injury model. A randomized, double-blind, placebo-controlled, crossover trial with an enriched enrollment design. In: PLoS ONE. 2020 ; Vol. 15, No. 11.

Bibtex

@article{b3147a4df8594f139671e6fa33bc9b62,
title = "High-dose naloxone: Effects by late administration on pain and hyperalgesia following a human heat injury model. A randomized, double-blind, placebo-controlled, crossover trial with an enriched enrollment design",
abstract = "Severe chronic postsurgical pain has a prevalence of 4-10% in the surgical population. The underlying nociceptive mechanisms have not been well characterized. Following the late resolution phase of an inflammatory injury, high-dose μ-opioid-receptor inverse agonists reinstate hypersensitivity to nociceptive stimuli. This unmasking of latent pain sensitization has been a consistent finding in rodents while only observed in a limited number of human volunteers. Latent sensitization could be a potential triggering venue in chronic postsurgical pain. The objective of the present trial was in detail to examine the association between injury-induced secondary hyperalgesia and naloxone-induced unmasking of latent sensitization. Healthy volunteers (n = 80) received a cutaneous heat injury (47°C, 420 s, 12.5 cm2). Baseline secondary hyperalgesia areas were assessed 1 h post-injury. Utilizing an enriched enrollment design, subjects with a magnitude of secondary hyperalgesia areas in the upper quartile ('high-sensitizers' [n = 20]) and the lower quartile ('low-sensitizers' [n = 20]) were selected for further study. In four consecutive experimental sessions (Sessions 1 to 4), the subjects at two sessions (Sessions 1 and 3) received a cutaneous heat injury followed 168 h later (Sessions 2 and 4) by a three-step target-controlled intravenous infusion of naloxone (3.25 mg/kg), or normal saline. Assessments of secondary hyperalgesia areas were made immediately before and stepwise during the infusions. Simple univariate statistics revealed no significant differences in secondary hyperalgesia areas between naloxone and placebo treatments (P = 0.215), or between 'high-sensitizers' and 'low-sensitizers' (P = 0.757). In a mixed-effects model, secondary hyperalgesia areas were significantly larger following naloxone as compared to placebo for 'high-sensitizers' (P < 0.001), but not 'low-sensitizers' (P = 0.651). Although we could not unequivocally demonstrate naloxone-induced reinstatement of heat injury-induced hyperalgesia, further studies in clinical postsurgical pain models are warranted.",
author = "Springborg, {Anders Deichmann} and Jensen, {Elisabeth Kj{\ae}r} and Mads Kreilgaard and Petersen, {Morten Aagaard} and Theodoros Papathanasiou and Lund, {Trine Meldgaard} and Taylor, {Bradley Kenneth} and Werner, {Mads Utke}",
year = "2020",
doi = "10.1371/journal.pone.0242169",
language = "English",
volume = "15",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

RIS

TY - JOUR

T1 - High-dose naloxone

T2 - Effects by late administration on pain and hyperalgesia following a human heat injury model. A randomized, double-blind, placebo-controlled, crossover trial with an enriched enrollment design

AU - Springborg, Anders Deichmann

AU - Jensen, Elisabeth Kjær

AU - Kreilgaard, Mads

AU - Petersen, Morten Aagaard

AU - Papathanasiou, Theodoros

AU - Lund, Trine Meldgaard

AU - Taylor, Bradley Kenneth

AU - Werner, Mads Utke

PY - 2020

Y1 - 2020

N2 - Severe chronic postsurgical pain has a prevalence of 4-10% in the surgical population. The underlying nociceptive mechanisms have not been well characterized. Following the late resolution phase of an inflammatory injury, high-dose μ-opioid-receptor inverse agonists reinstate hypersensitivity to nociceptive stimuli. This unmasking of latent pain sensitization has been a consistent finding in rodents while only observed in a limited number of human volunteers. Latent sensitization could be a potential triggering venue in chronic postsurgical pain. The objective of the present trial was in detail to examine the association between injury-induced secondary hyperalgesia and naloxone-induced unmasking of latent sensitization. Healthy volunteers (n = 80) received a cutaneous heat injury (47°C, 420 s, 12.5 cm2). Baseline secondary hyperalgesia areas were assessed 1 h post-injury. Utilizing an enriched enrollment design, subjects with a magnitude of secondary hyperalgesia areas in the upper quartile ('high-sensitizers' [n = 20]) and the lower quartile ('low-sensitizers' [n = 20]) were selected for further study. In four consecutive experimental sessions (Sessions 1 to 4), the subjects at two sessions (Sessions 1 and 3) received a cutaneous heat injury followed 168 h later (Sessions 2 and 4) by a three-step target-controlled intravenous infusion of naloxone (3.25 mg/kg), or normal saline. Assessments of secondary hyperalgesia areas were made immediately before and stepwise during the infusions. Simple univariate statistics revealed no significant differences in secondary hyperalgesia areas between naloxone and placebo treatments (P = 0.215), or between 'high-sensitizers' and 'low-sensitizers' (P = 0.757). In a mixed-effects model, secondary hyperalgesia areas were significantly larger following naloxone as compared to placebo for 'high-sensitizers' (P < 0.001), but not 'low-sensitizers' (P = 0.651). Although we could not unequivocally demonstrate naloxone-induced reinstatement of heat injury-induced hyperalgesia, further studies in clinical postsurgical pain models are warranted.

AB - Severe chronic postsurgical pain has a prevalence of 4-10% in the surgical population. The underlying nociceptive mechanisms have not been well characterized. Following the late resolution phase of an inflammatory injury, high-dose μ-opioid-receptor inverse agonists reinstate hypersensitivity to nociceptive stimuli. This unmasking of latent pain sensitization has been a consistent finding in rodents while only observed in a limited number of human volunteers. Latent sensitization could be a potential triggering venue in chronic postsurgical pain. The objective of the present trial was in detail to examine the association between injury-induced secondary hyperalgesia and naloxone-induced unmasking of latent sensitization. Healthy volunteers (n = 80) received a cutaneous heat injury (47°C, 420 s, 12.5 cm2). Baseline secondary hyperalgesia areas were assessed 1 h post-injury. Utilizing an enriched enrollment design, subjects with a magnitude of secondary hyperalgesia areas in the upper quartile ('high-sensitizers' [n = 20]) and the lower quartile ('low-sensitizers' [n = 20]) were selected for further study. In four consecutive experimental sessions (Sessions 1 to 4), the subjects at two sessions (Sessions 1 and 3) received a cutaneous heat injury followed 168 h later (Sessions 2 and 4) by a three-step target-controlled intravenous infusion of naloxone (3.25 mg/kg), or normal saline. Assessments of secondary hyperalgesia areas were made immediately before and stepwise during the infusions. Simple univariate statistics revealed no significant differences in secondary hyperalgesia areas between naloxone and placebo treatments (P = 0.215), or between 'high-sensitizers' and 'low-sensitizers' (P = 0.757). In a mixed-effects model, secondary hyperalgesia areas were significantly larger following naloxone as compared to placebo for 'high-sensitizers' (P < 0.001), but not 'low-sensitizers' (P = 0.651). Although we could not unequivocally demonstrate naloxone-induced reinstatement of heat injury-induced hyperalgesia, further studies in clinical postsurgical pain models are warranted.

U2 - 10.1371/journal.pone.0242169

DO - 10.1371/journal.pone.0242169

M3 - Journal article

C2 - 33180816

VL - 15

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 11

M1 - e0242169

ER -

ID: 251574576