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Cited by 5Pain Management and Placebo EffectFibromyalgia and Chronic Fatigue Syndrome ResearchPain Mechanisms and Treatments

Nocebo hyperalgesia in patients with fibromyalgia and healthy controls: an experimental investigation of conditioning and extinction processes at baseline and 1-month follow-up

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Karacaoglu, Merve, Peerdeman, Kaya J., Numans, Mattijs E., Stolk, Martha R., Meijer, Simone, Klinger, Regine, Veldhuijzen, Dieuwke S., van Middendorp, Henriët +1 more·2023·The Journal of Pain
DOI 10.1016/j.jpain.2023.05.003
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Abstract

Nocebo effects are adverse treatment outcomes that are not ascribed to active treatment components. Potentially, their magnitude might be higher in patients with chronic pain compared to healthy controls since patients likely experience treatment failure more frequently. The current study investigated group differences in the induction and extinction of nocebo effects on pressure pain at baseline (N = 69) and 1-month follow-up (N = 56) in female patients with fibromyalgia and matched healthy controls. Nocebo effects were first experimentally induced via classical conditioning combined with instructions on the pain-increasing function of a sham transcutaneous electrical nerve stimulation device, then decreased via extinction. One month later, the same procedures were repeated to explore their stability. Results suggest that nocebo effects were induced in the healthy control group during baseline and follow-up. In the patient group, nocebo effects were only induced during follow-up, without clear group differences. Extinction was only observed during baseline in the healthy control group. Further comparisons of nocebo effects and extinction indicated no significant changes across sessions, possibly suggesting their overall magnitudes were stable over time and across groups. In conclusion, contrary to our expectations, patients with fibromyalgia did not have stronger nocebo hyperalgesia; instead, they might be less responsive to nocebo manipulations than healthy controls. PERSPECTIVE: The current study is the first to investigate group differences in experimentally manipulated nocebo hyperalgesia between chronic pain and healthy populations at baseline and 1-month follow-up. Since nocebo effects are common in clinical settings, their investigation in different populations is essential to explain and minimize their adverse effects during treatment.

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  • The magnitude of experimentally induced nocebo hyperalgesia was not large (M = 0.23, SD = 0.97).

    “Nocebo hyperalgesia was induced experimentally (as the mean score was above 0); however, its magnitude was not large ( M = 0.23, SD = 0.97), while it also showed the smallest mean vari ability between patients compared to self-reported expectancy-related factors (Table 1) [19].”

    From Nocebo hyperalgesia and other expectancy-related factors in daily fibromyalgia pain: Combining experimental and electronic diary methods (2024) · cites this paper as [19]

    The Induction of Nocebo Effects in Session 1 section reports small positive nocebo difference scores, including 0.19 (SD 0.74) for patients, so the source supports the general description of a small experimentally induced effect. It does not report M = 0.23, SD = 0.97; it also says the patient-group difference was not statistically significant. The citing sentence points to its own Table 1 for the numerical summary. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Nocebo hyperalgesia showed the smallest mean variability between patients compared to self-reported expectancy-related factors.

    “Nocebo hyperalgesia was induced experimentally (as the mean score was above 0); however, its magnitude was not large ( M = 0.23, SD = 0.97), while it also showed the smallest mean vari ability between patients compared to self-reported expectancy-related factors (Table 1) [19].”

    From Nocebo hyperalgesia and other expectancy-related factors in daily fibromyalgia pain: Combining experimental and electronic diary methods (2024) · cites this paper as [19]

    Table 3 (Induction of Nocebo Effects in Session 1; page unavailable) reports a patient nocebo difference score of 0.19 (SD 0.74), while Table 2 (Descriptive Statistics; page unavailable) reports an SD of 2.33 for patients’ self-reported perceived effect of the device on pain. The paper does not establish that nocebo hyperalgesia had the smallest variability among expectancy-related factors, and its reported patient score does not match the citing sentence’s M = 0.23, SD = 0.97. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Nocebo hyperalgesia was induced experimentally, as the mean score was above 0.

    “Nocebo hyperalgesia was induced experimentally (as the mean score was above 0); however, its magnitude was not large ( M = 0.23, SD = 0.97), while it also showed the smallest mean vari ability between patients compared to self-reported expectancy-related factors (Table 1) [19].”

    From Nocebo hyperalgesia and other expectancy-related factors in daily fibromyalgia pain: Combining experimental and electronic diary methods (2024) · cites this paper as [19]

    In Table 3 (page unavailable), the experimental-minus-control pain difference was above zero for patients and healthy controls. But the Induction of Nocebo Effects in Session 1 section reports a significant effect in healthy controls, not in patients (P = .13). Thus a positive patient mean alone does not establish that nocebo hyperalgesia was induced in patients. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • In the lab, small nocebo hyperalgesia effects on pressure pain were induced [19].

    “In the lab, small nocebo hyperalgesia effects on pressure pain were induced [19].”

    From Nocebo hyperalgesia and other expectancy-related factors in daily fibromyalgia pain: Combining experimental and electronic diary methods (2024) · cites this paper as [19]

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Authors
Karacaoglu, M., Peerdeman, K. J., Numans, M. E., Stolk, M. R., Meijer, S., Klinger, R., Veldhuijzen, D. S., van Middendorp, H., & Evers, A. W. M.
Affiliations
  • Leiden University (NL)
  • Leiden University Medical Center (NL)
  • University Medical Center Hamburg-Eppendorf (DE)
Corresponding author
Karacaoglu, Merve
ORCID
Venue
The Journal of Pain
Publisher
Elsevier BV
Published
2023-09
Volume
24
Issue
9
Pages
1696-1711
ISSN
1526-5900 (ISSN-L)
DOI
10.1016/j.jpain.2023.05.003
OpenAlex
W4377011906
Cited by
5
References
55
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 1
FWCI
0.75
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Pain (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Leiden Repository (Leiden University) (submittedVersion, cc-by)
  • Research Repository (Delft University of Technology) (submittedVersion, cc-by)
Funders
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (45316004)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
  • Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
nocebo hyperalgesia, fibromyalgia, nocebo effect, classical conditioning, extinction, pressure pain, chronic pain, transcutaneous electrical nerve stimulation, sham stimulation, placebo effect, female patients
MeSH terms
Female, Fibromyalgia, Follow-Up Studies, Humans, Hyperalgesia, Chronic Pain, Nocebo Effect

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