Nocebo Hyperalgesia in Patients With Fibromyalgia and Healthy Controls: An Experimental Investigation of Conditioning and Extinction Processes at Baseline and 1-Month Follow-up

Merve Karacaoglu; Kaya J Peerdeman; Mattijs E Numans; Martha R Stolk; Simone Meijer; Regine Klinger; Dieuwke S Veldhuijzen; Henriët van Middendorp; Andrea W M Evers

doi:10.1016/j.jpain.2023.05.003

Nocebo Hyperalgesia in Patients With Fibromyalgia and Healthy Controls: An Experimental Investigation of Conditioning and Extinction Processes at Baseline and 1-Month Follow-up

J Pain. 2023 Sep;24(9):1696-1711. doi: 10.1016/j.jpain.2023.05.003. Epub 2023 May 23.

Authors

Merve Karacaoglu¹, Kaya J Peerdeman¹, Mattijs E Numans², Martha R Stolk³, Simone Meijer¹, Regine Klinger⁴, Dieuwke S Veldhuijzen¹, Henriët van Middendorp¹, Andrea W M Evers⁵

Affiliations

¹ Health, Medical and Neuropsychology unit, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden, The Netherlands.
² Public Health and Primary Care Department/LUMC-Campus Den Haag, Leiden University Medical Center, The Hague, The Netherlands.
³ Health, Medical and Neuropsychology unit, Leiden University, Leiden, The Netherlands.
⁴ Center for Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁵ Health, Medical and Neuropsychology unit, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden, The Netherlands; Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands; Medical Delta, Erasmus University Rotterdam, Leiden University & Delft University of Technology, Delft, The Netherlands.

PMID: 37196928
DOI: 10.1016/j.jpain.2023.05.003

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.

Keywords: Nocebo effect; classical conditioning; fibromyalgia; hyperalgesia; pressure pain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chronic Pain* / therapy
Female
Fibromyalgia* / therapy
Follow-Up Studies
Humans
Hyperalgesia / therapy
Nocebo Effect