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The role of oxytocin and sex in analgesic placebo-response: exploratory analysis from a sham randomized clinical trial in chronic back-pain patients

2025-10-17Research article Open access
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dc.contributor.authorMendelson-Keypur, Rinat
dc.contributor.authorShani, Adi
dc.contributor.authorGranot, Michal
dc.contributor.authorAgostinho, Mariana Ribolhos
dc.contributor.authorPaltzur, Eilam
dc.contributor.authorTreister, Roi
dc.contributor.authorRahamimov, Nimrod
dc.date.accessioned2025-11-12T10:41:03Z
dc.date.available2025-11-12T10:41:03Z
dc.date.issued2025-10-17
dc.description.abstractBackground: Several studies suggest that exogenous oxytocin nasal spray may enhance placebo analgesia in healthy volunteers and experimental pain models, although the findings remain mixed. The oxytocin placebo hypothesis suggests that increased oxytocin levels trigger a cascade of brain processes that boost positive expectations and augment the placebo response. Since endogenous oxytocin secretion has been found to increase during positive interactions, we hypothesized that changes in endogenous oxytocin levels will affect placebo analgesia in chronic-back-pain patients. Given the role sex has in both placebo analgesia and oxytocin secretion, we hypothesized that the response magnitude will differ by sex. Methods: Chronic-back-pain patients (n = 112) were prospectively recruited and received placebo injections. The placebo response was calculated as the change in the back-pain Visual Analog Score (VAS), and changes between pre- and post-injection salivary oxytocin levels were measured. The effect of sex and changes in oxytocin levels on pain reduction was calculated using two-way analysis of variance (ANCOVA). Results: Oxytocin levels decreased in 62.5% of participants and increased in 37.5%. Increased oxytocin levels were associated with greater pain reduction than decreased oxytocin levels (p = 0.024). Females exhibited greater pain reduction than males (p = 0.034). No interaction between the oxytocin change pattern and sex was observed. Conclusions: This study demonstrates that following a placebo injection, patients suffering from chronic back pain, who exhibited an increase in endogenous oxytocin levels, showed a higher placebo response. Females had a greater placebo response, but this was not associated with an endogenous oxytocin change. These results provide initial support for the oxytocin placebo hypothesis.eng
dc.identifier.citationMendelson-Keypur, R., Shani, A., Granot, M., & Agostinho, M. R. et al. (2025). The role of oxytocin and sex in analgesic placebo-response: exploratory analysis from a sham randomized clinical trial in chronic back-pain patients. Journal of Clinical Medicine, 14(20), Article 7348. https://doi.org/10.3390/jcm14207348
dc.identifier.doi10.3390/jcm14207348
dc.identifier.eid105020297691
dc.identifier.issn2077-0383
dc.identifier.other1b384161-684c-45d8-9e8b-f6b01950b4dd
dc.identifier.pmcPMC12564996
dc.identifier.pmid41156217
dc.identifier.urihttp://hdl.handle.net/10400.14/55620
dc.identifier.wos001601736300001
dc.language.isoeng
dc.peerreviewedyes
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBiological sex
dc.subjectChronic back pain
dc.subjectOxytocin
dc.subjectPlacebo analgesia
dc.subjectPlacebo response
dc.titleThe role of oxytocin and sex in analgesic placebo-response: exploratory analysis from a sham randomized clinical trial in chronic back-pain patientseng
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.issue20
oaire.citation.titleJournal of Clinical Medicine
oaire.citation.volume14
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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