Nocebo Hyperalgesia, Partial Reinforcement, and Extinction
Open accessAbstract
Unlabelled Many studies have found evidence of conditioning-induced nocebo hyperalgesia. However, these studies have exclusively involved continuous reinforcement (CRF) schedules. Thus, it is currently unknown whether nocebo hyperalgesia can result after partial reinforcement (PRF). We tested this using electrodermal pain stimulation in healthy volunteers. Undergraduates (N = 135) received nocebo treatment under the guise of a hyperalgesic. Participants were randomly allocated to CRF, PRF, or control (no conditioning). Conditioning involved surreptitiously increasing pain stimulation on nocebo trials relative to control trials. During training, the CRF group always had the nocebo paired with the surreptitious pain increase, whereas the PRF group experienced the increase on only 62.5% of nocebo trials. In the test phase, pain stimulation was equivalent across nocebo and control trials. PRF was sufficient to induce nocebo hyperalgesia; however, this was weaker than CRF. Nocebo hyperalgesia failed to extinguish irrespective of the training schedule. Additional assessment of expectancies indicated strong concordance between expectancy and nocebo hyperalgesia. Overall, these findings suggest that once established, nocebo hyperalgesia may be difficult to disrupt. PRF may be a novel method of reducing the intensity of nocebo hyperalgesia in the clinic, which may be particularly important given its persistence.Perspective This study provides novel evidence that partial reinforcement results in weaker nocebo hyperalgesia than continuous reinforcement and that nocebo hyperalgesia fails to extinguish, irrespective of the training schedule. As a result, partial reinforcement may serve as a method for reducing the intensity of nocebo hyperalgesia in the clinic.
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Nocebo responses are stronger than placebo responses.
“Nocebo responses are stronger, more difficult to extinguish and less sensitive to sensory evidence than placebo responses8,18–20.”
From Boundary effects of expectation in human pain perception (2019) · cites this paper as [20]
Nocebo responses are more difficult to extinguish than placebo responses.
“Nocebo responses are stronger, more difficult to extinguish and less sensitive to sensory evidence than placebo responses8,18–20.”
From Boundary effects of expectation in human pain perception (2019) · cites this paper as [20]
Nocebo responses are less sensitive to sensory evidence than placebo responses.
“Nocebo responses are stronger, more difficult to extinguish and less sensitive to sensory evidence than placebo responses8,18–20.”
From Boundary effects of expectation in human pain perception (2019) · cites this paper as [20]
Because expectations of low pain are more easily extinguished and more sensitive to sensory evidence, the positive PE condition was more vulnerable to an unmeasured variable than the negative PE condition.
“It is plausible that because expectations of low pain are more easily extinguished and more sensitive to sensory evidence18–21, the corresponding positive PE condition was more vulnerable to an unmeasured variable than the negative PE condition.”
From Boundary effects of expectation in human pain perception (2019) · cites this paper as [20]
Expectations about side effects that produce nocebo effects can be induced through verbal suggestion or written information, including information provided during the informed consent process about potential adverse events.
“Expectations about side effects, that produce nocebo effects, can be induced through verbal suggestion15 or written information,20 the latter including information provided during the informed consent process about potential adverse events.7”
From Nocebo and pain: an overview of the psychoneurobiological mechanisms (2017) · cites this paper as [20]
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References 40 · Cited by 98
- Authors
- Colagiuri, B., Quinn, V. F., & Colloca, L.
- Affiliations
- The University of Sydney (AU)
- University of Maryland, Baltimore (US)
- Corresponding author
- Colagiuri, Ben
- Venue
- The Journal of Pain
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 16
- Issue
- 10
- Pages
- 995-1004
- ISSN
- 1526-5900 (ISSN-L)
- OpenAlex
- W2130063504
- Cited by
- 98
- References
- 40
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 11 · 2023: 13 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 15 · 2018: 8 · 2017: 9 · 2016: 2 · 2015: 1
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Pain (publishedVersion)
- PubMed (publishedVersion)
- The Sydney eScholarship Repository (The University of Sydney) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- nocebo hyperalgesia, partial reinforcement, continuous reinforcement, extinction, pain anticipation, pain conditioning
- MeSH terms
- Adolescent, Adult, Transcutaneous Electric Nerve Stimulation, Female, Humans, Hyperalgesia, Male, Pain, Random Allocation, Reinforcement, Psychology, Reinforcement Schedule, Young Adult, Healthy Volunteers, Nocebo Effect
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