Background & Aims

Chronic back-pain presents a significant healthcare challenge. Better understanding the factors contributing to changes in back pain is needed. Placebo analgesia offers opportunity to learn about endogenous pain modulation mechanisms. Oxytocin (OT), known for its role in social bonding and pain modulation, may modulate the placebo-response, with potential gender-specific effects.
The aim of the current project was to assess if changes in endogenous Oxytocin levels and gender will be associated with changes in pain following saline injection plus verbal suggestion in a cohort of chronic back pain patients.

Methods

In this prospective randomized double blinded study, 113 chronic back-pain patients were recruited and received one of two placebo injections. Placebo-response was calculated as the delta of self-reported pain before and 30 minutes after a placebo injection. Salivary OT levels were measured before and after the intervention using an Enzyme-Linked Immunosorbent Assay (ELISA) testing. Participants were categorized based on changes in OT levels (positive/negative) and gender. A two-way ANOVA examined the effects of OT changes and gender on placebo response.

Results

Following the placebo injection, pain significantly decreased (mean decrease: 19.7±17.5, p<0.001). Salivary OT levels declined post-intervention (Z=-2.604, p=0.009), with women more likely to exhibit decreased OT levels (?²=8.3, p=0.004) than men. While both OT changes and gender independently demonstrated main effects, (p=0.021 and p=0.039, respectively), their interaction did not significantly impact outcomes (p=0.420).

Conclusions

Two main effects emerged: (1) Participants with an increase in Oxytocin levels following placebo administration exhibited a greater placebo-response; (2) Women demonstrated larger placebo-response than men, but not in interactive fashion. These results highlight the independent role of Oxytocin and gender in pain modulation in the context of placebo research.

References

[1] Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet 2021;397:2082–2097.
[2] Itskovich E, Bowling DL, Garner JP, Parker KJ. Oxytocin and the social facilitation of placebo effects. Mol Psychiatry 2022;27:2640–2649.
[3] Medoff ZM, Colloca L. Placebo analgesia: understanding the mechanisms. Pain Manag 2015;5:89–96.
[4] Shafir R, Olson E, Colloca L. The neglect of sex: A call to action for including sex as a biological variable in placebo and nocebo research. Contemp Clin Trials 2022;116:106734.
[5] Tracy LM, Georgiou-Karistianis N, Gibson SJ, Giummarra MJ. Oxytocin and the modulation of pain experience: Implications for chronic pain management. Neurosci Biobehav Rev 2015;55:53–67.

Presenting Author

Adi Shani

Poster Authors

Adi Shani

MA, Doctoral student

The Cheryl Spencer Department of Nursing, University of Haifa, Galilee Medical Center, Naharyia

Lead Author

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Rinat Mendelson-Keypur (BA)

Faculty of Social Sciences Department of Psychology, University of Haifa

Lead Author

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Mariana Agostinho

(MA)

The Cheryl Spencer Department of Nursing, University of Haifa

Lead Author

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Michal Granot (PhD)

The Cheryl Spencer Department of Nursing, University of Haifa

Lead Author

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Nimrod Rahamimov (MD)

Galilee Medical Center, Naharyia; Faculty of Medicine, Bar Ilan Medical School, Tsfat

Lead Author

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Roi Treister PhD

The Cheryl Spencer Department of Nursing, University of Haifa

Lead Author

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Topics

  • Gender/Sex Differences