Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers–A randomized, double-blinded, placebo-controlled study

Autores
Biurrun Manresa, José Alberto; Schliessbach, Jürg; Vuilleumier, Pascal H.; Müller, Monika; Musshoff, Frank; Stamer, Ulrike; Stüber, Frank; Arendt Nielsen, Lars; Curatolo, Michele
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: There is increasing evidence for oxytocin as a neurotransmitter in spinal nociceptive processes. Hypothalamic oxytocinergic neurons project to the spinal dorsal horn, where they activate GABA-ergic inhibitory interneurons. The present study tested whether the long-acting oxytocin-analogue carbetocin has anti-nociceptive effects in multi-modal experimental pain in humans. Methods: Twenty-five male volunteers received carbetocin 100 mcg and placebo (0.9% NaCl) on two different sessions in a randomized, double-blinded, cross-over design. Multi-modal quantitative sensory testing (QST) including a model of capsaicin-induced hyperalgesia and allodynia were performed at baseline and at 10, 60 and 120 min after drug administration. QST data were analysed using mixed linear and logistic regression models. Carbetocin plasma concentrations and oxytocin receptor genotypes were quantified and assessed in an exploratory fashion. Results: An anti-nociceptive effect of carbetocin was observed on intramuscular electrical temporal summation (estimated difference: 1.26 mA, 95% CI 1.01 to 1.56 mA, p =.04) and single-stimulus electrical pain thresholds (estimated difference: 1.21 mA, 95% CI 1.0 to 1.47 mA, p =.05). Furthermore, the area of capsaicin-induced allodynia was reduced after carbetocin compared to placebo (estimated difference: −6.5 cm2, 95% CI −9.8 to −3.2 cm2, p <.001). Conclusions: This study provides evidence of an anti-nociceptive effect of carbetocin on experimental pain in humans. Significance: This study provides evidence of the anti-nociceptive effect of intravenous administration of the oxytocin agonist carbetocin in healthy male volunteers.
Fil: Biurrun Manresa, José Alberto. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; Argentina
Fil: Schliessbach, Jürg. Bern University Hospital; Suiza
Fil: Vuilleumier, Pascal H.. Bern University Hospital; Suiza
Fil: Müller, Monika. Bern University Hospital; Suiza
Fil: Musshoff, Frank. No especifíca; . Bern University Hospital; Suiza
Fil: Stamer, Ulrike. Bern University Hospital; Suiza
Fil: Stüber, Frank. Bern University Hospital; Suiza
Fil: Arendt Nielsen, Lars. No especifíca;
Fil: Curatolo, Michele. University of Washington; Estados Unidos
Materia
Hyperalgesia
Interneurons
Oxytocin analogs
Spinal cord dorsal horn
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/173424
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/173424
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers–A randomized, double-blinded, placebo-controlled studyBiurrun Manresa, José AlbertoSchliessbach, JürgVuilleumier, Pascal H.Müller, MonikaMusshoff, FrankStamer, UlrikeStüber, FrankArendt Nielsen, LarsCuratolo, MicheleHyperalgesiaInterneuronsOxytocin analogsSpinal cord dorsal hornhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: There is increasing evidence for oxytocin as a neurotransmitter in spinal nociceptive processes. Hypothalamic oxytocinergic neurons project to the spinal dorsal horn, where they activate GABA-ergic inhibitory interneurons. The present study tested whether the long-acting oxytocin-analogue carbetocin has anti-nociceptive effects in multi-modal experimental pain in humans. Methods: Twenty-five male volunteers received carbetocin 100 mcg and placebo (0.9% NaCl) on two different sessions in a randomized, double-blinded, cross-over design. Multi-modal quantitative sensory testing (QST) including a model of capsaicin-induced hyperalgesia and allodynia were performed at baseline and at 10, 60 and 120 min after drug administration. QST data were analysed using mixed linear and logistic regression models. Carbetocin plasma concentrations and oxytocin receptor genotypes were quantified and assessed in an exploratory fashion. Results: An anti-nociceptive effect of carbetocin was observed on intramuscular electrical temporal summation (estimated difference: 1.26 mA, 95% CI 1.01 to 1.56 mA, p =.04) and single-stimulus electrical pain thresholds (estimated difference: 1.21 mA, 95% CI 1.0 to 1.47 mA, p =.05). Furthermore, the area of capsaicin-induced allodynia was reduced after carbetocin compared to placebo (estimated difference: −6.5 cm2, 95% CI −9.8 to −3.2 cm2, p <.001). Conclusions: This study provides evidence of an anti-nociceptive effect of carbetocin on experimental pain in humans. Significance: This study provides evidence of the anti-nociceptive effect of intravenous administration of the oxytocin agonist carbetocin in healthy male volunteers.Fil: Biurrun Manresa, José Alberto. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Schliessbach, Jürg. Bern University Hospital; SuizaFil: Vuilleumier, Pascal H.. Bern University Hospital; SuizaFil: Müller, Monika. Bern University Hospital; SuizaFil: Musshoff, Frank. No especifíca; . Bern University Hospital; SuizaFil: Stamer, Ulrike. Bern University Hospital; SuizaFil: Stüber, Frank. Bern University Hospital; SuizaFil: Arendt Nielsen, Lars. No especifíca;Fil: Curatolo, Michele. University of Washington; Estados UnidosWiley2021-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/173424Biurrun Manresa, José Alberto; Schliessbach, Jürg; Vuilleumier, Pascal H.; Müller, Monika; Musshoff, Frank; et al.; Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers–A randomized, double-blinded, placebo-controlled study; Wiley; European Journal of Pain; 4-2021; 1-341090-3801CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/ejp.1781info:eu-repo/semantics/altIdentifier/doi/10.1002/ejp.1781info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:47:38Zoai:ri.conicet.gov.ar:11336/173424instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:47:38.41CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers–A randomized, double-blinded, placebo-controlled study
title Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers–A randomized, double-blinded, placebo-controlled study
spellingShingle Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers–A randomized, double-blinded, placebo-controlled study
Biurrun Manresa, José Alberto
Hyperalgesia
Interneurons
Oxytocin analogs
Spinal cord dorsal horn
title_short Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers–A randomized, double-blinded, placebo-controlled study
title_full Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers–A randomized, double-blinded, placebo-controlled study
title_fullStr Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers–A randomized, double-blinded, placebo-controlled study
title_full_unstemmed Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers–A randomized, double-blinded, placebo-controlled study
title_sort Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers–A randomized, double-blinded, placebo-controlled study
dc.creator.none.fl_str_mv Biurrun Manresa, José Alberto
Schliessbach, Jürg
Vuilleumier, Pascal H.
Müller, Monika
Musshoff, Frank
Stamer, Ulrike
Stüber, Frank
Arendt Nielsen, Lars
Curatolo, Michele
author Biurrun Manresa, José Alberto
author_facet Biurrun Manresa, José Alberto
Schliessbach, Jürg
Vuilleumier, Pascal H.
Müller, Monika
Musshoff, Frank
Stamer, Ulrike
Stüber, Frank
Arendt Nielsen, Lars
Curatolo, Michele
author_role author
author2 Schliessbach, Jürg
Vuilleumier, Pascal H.
Müller, Monika
Musshoff, Frank
Stamer, Ulrike
Stüber, Frank
Arendt Nielsen, Lars
Curatolo, Michele
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hyperalgesia
Interneurons
Oxytocin analogs
Spinal cord dorsal horn
topic Hyperalgesia
Interneurons
Oxytocin analogs
Spinal cord dorsal horn
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: There is increasing evidence for oxytocin as a neurotransmitter in spinal nociceptive processes. Hypothalamic oxytocinergic neurons project to the spinal dorsal horn, where they activate GABA-ergic inhibitory interneurons. The present study tested whether the long-acting oxytocin-analogue carbetocin has anti-nociceptive effects in multi-modal experimental pain in humans. Methods: Twenty-five male volunteers received carbetocin 100 mcg and placebo (0.9% NaCl) on two different sessions in a randomized, double-blinded, cross-over design. Multi-modal quantitative sensory testing (QST) including a model of capsaicin-induced hyperalgesia and allodynia were performed at baseline and at 10, 60 and 120 min after drug administration. QST data were analysed using mixed linear and logistic regression models. Carbetocin plasma concentrations and oxytocin receptor genotypes were quantified and assessed in an exploratory fashion. Results: An anti-nociceptive effect of carbetocin was observed on intramuscular electrical temporal summation (estimated difference: 1.26 mA, 95% CI 1.01 to 1.56 mA, p =.04) and single-stimulus electrical pain thresholds (estimated difference: 1.21 mA, 95% CI 1.0 to 1.47 mA, p =.05). Furthermore, the area of capsaicin-induced allodynia was reduced after carbetocin compared to placebo (estimated difference: −6.5 cm2, 95% CI −9.8 to −3.2 cm2, p <.001). Conclusions: This study provides evidence of an anti-nociceptive effect of carbetocin on experimental pain in humans. Significance: This study provides evidence of the anti-nociceptive effect of intravenous administration of the oxytocin agonist carbetocin in healthy male volunteers.
Fil: Biurrun Manresa, José Alberto. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; Argentina
Fil: Schliessbach, Jürg. Bern University Hospital; Suiza
Fil: Vuilleumier, Pascal H.. Bern University Hospital; Suiza
Fil: Müller, Monika. Bern University Hospital; Suiza
Fil: Musshoff, Frank. No especifíca; . Bern University Hospital; Suiza
Fil: Stamer, Ulrike. Bern University Hospital; Suiza
Fil: Stüber, Frank. Bern University Hospital; Suiza
Fil: Arendt Nielsen, Lars. No especifíca;
Fil: Curatolo, Michele. University of Washington; Estados Unidos
description Background: There is increasing evidence for oxytocin as a neurotransmitter in spinal nociceptive processes. Hypothalamic oxytocinergic neurons project to the spinal dorsal horn, where they activate GABA-ergic inhibitory interneurons. The present study tested whether the long-acting oxytocin-analogue carbetocin has anti-nociceptive effects in multi-modal experimental pain in humans. Methods: Twenty-five male volunteers received carbetocin 100 mcg and placebo (0.9% NaCl) on two different sessions in a randomized, double-blinded, cross-over design. Multi-modal quantitative sensory testing (QST) including a model of capsaicin-induced hyperalgesia and allodynia were performed at baseline and at 10, 60 and 120 min after drug administration. QST data were analysed using mixed linear and logistic regression models. Carbetocin plasma concentrations and oxytocin receptor genotypes were quantified and assessed in an exploratory fashion. Results: An anti-nociceptive effect of carbetocin was observed on intramuscular electrical temporal summation (estimated difference: 1.26 mA, 95% CI 1.01 to 1.56 mA, p =.04) and single-stimulus electrical pain thresholds (estimated difference: 1.21 mA, 95% CI 1.0 to 1.47 mA, p =.05). Furthermore, the area of capsaicin-induced allodynia was reduced after carbetocin compared to placebo (estimated difference: −6.5 cm2, 95% CI −9.8 to −3.2 cm2, p <.001). Conclusions: This study provides evidence of an anti-nociceptive effect of carbetocin on experimental pain in humans. Significance: This study provides evidence of the anti-nociceptive effect of intravenous administration of the oxytocin agonist carbetocin in healthy male volunteers.
publishDate 2021
dc.date.none.fl_str_mv 2021-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/173424
Biurrun Manresa, José Alberto; Schliessbach, Jürg; Vuilleumier, Pascal H.; Müller, Monika; Musshoff, Frank; et al.; Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers–A randomized, double-blinded, placebo-controlled study; Wiley; European Journal of Pain; 4-2021; 1-34
1090-3801
CONICET Digital
CONICET
url http://hdl.handle.net/11336/173424
identifier_str_mv Biurrun Manresa, José Alberto; Schliessbach, Jürg; Vuilleumier, Pascal H.; Müller, Monika; Musshoff, Frank; et al.; Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers–A randomized, double-blinded, placebo-controlled study; Wiley; European Journal of Pain; 4-2021; 1-34
1090-3801
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/ejp.1781
info:eu-repo/semantics/altIdentifier/doi/10.1002/ejp.1781
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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