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Cited by 109Pain Management and Placebo EffectMigraine and Headache StudiesPain Mechanisms and Treatments

Nocebo and placebo modulation of hypobaric hypoxia headache involves the cyclooxygenase-prostaglandins pathway

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Benedetti, Fabrizio, Durando, Jennifer, Vighetti, Sergio·2014·Pain
DOI 10.1016/j.pain.2014.01.016
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Abstract

Nocebo and placebo effects have been found to modulate several neurochemical systems, such as cholecystokinin, endogenous opioids, and endocannabinoids. Here we show that also the cyclooxygenase-prostaglandins pathway can be modulated by both nocebos and placebos. In fact, we found that negative expectation, the crucial element of the nocebo effect, about headache pain led to the enhancement of the cyclooxygenase-prostaglandins pathway, which, in turn, induced pain worsening. As an experimental model, we studied hypobaric hypoxia headache at high altitude in 2 populations of subjects. Whereas the experimental nocebo group received negative information by a single individual who was informed about the risk of headache, the control group did not know about the possible occurrence of headache. We found a significant increase in headache and salivary prostaglandins and thromboxane in the nocebo group compared to the control group, suggesting that negative expectations enhance cyclooxygenase activity. In addition, placebo administration to headache sufferers at high altitude inhibited the nocebo-related component of pain and prostaglandins synthesis, which indicates that the cyclooxygenase pathway can be modulated by both nocebos and placebos. Our results show for the first time how nocebos and placebos affect the synthesis of prostaglandins, which represent an important target of analgesic drugs, thus emphasizing once again the notion that placebos and drugs may use common biochemical pathways.

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  • Direct comparisons of placebo and nocebo effects are rare.

    “To date, only a few studies have directly compared placebo and nocebo effects.”

    From Distinct neural representations of placebo and nocebo effects (2015) · cites this paper as Benedetti et al., 2014

  • Behavioral measures alone have been used in most direct comparisons of placebo and nocebo effects.

    “Most of these studies have involved behavioral measures only (Benedetti et al., 2014; Benedetti et al., 2003; Colloca et al., 2010; Colloca et al., 2008).”

    From Distinct neural representations of placebo and nocebo effects (2015) · cites this paper as Benedetti et al., 2014

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Authors
Benedetti, F., Durando, J., & Vighetti, S.
Affiliations
University of Turin (IT)
Corresponding author
Benedetti, Fabrizio
ORCID
Benedetti, Fabrizio
Venue
Pain
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2014-05
Volume
155
Issue
5
Pages
921-928
ISSN
0304-3959 (ISSN-L)
DOI
10.1016/j.pain.2014.01.016
OpenAlex
W2066630292
Cited by
109
References
37
Citations by year
2026: 4 · 2025: 7 · 2024: 4 · 2023: 11 · 2022: 4 · 2021: 13 · 2020: 15 · 2019: 11 · 2018: 14 · 2017: 5 · 2016: 7 · 2015: 10 · 2014: 4
FWCI
4.82
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Pain (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
Funders
  • Compagnia di San Paolo
  • Università degli Studi di Torino
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
  • Health Sciences › Medicine › Psychiatry and Mental health › Migraine and Headache Studies
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
nocebo effect, placebo effect, cyclooxygenase, prostaglandins, thromboxane, negative expectations, high altitude, salivary biomarkers, pain modulation, placebo analgesia
MeSH terms
Hypoxia, Female, Headache, Humans, Hydrocortisone, Male, Prostaglandin-Endoperoxide Synthases, Prostaglandins, Saliva, Placebo Effect, Young Adult, Nocebo Effect

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