Highlights
- •Nocebo hyperalgesia can be established via conditioning.
- •Pre-exposing individuals to treatment cues inhibits conditioned nocebo hyperalgesia.
- •Overshadowing with audio-visual cues did not reduce conditioned nocebo hyperalgesia.
- •Pre-exposure may be an effective method of reducing nocebo hyperalgesia clinically.
Abstract
Nocebo hyperalgesia is a pervasive problem that significantly adds to the burden of
pain. Conditioning is a key mechanism of nocebo hyperalgesia and recent evidence indicates
that, once established, nocebo hyperalgesia is resistant to extinction. This means
that preventive strategies are critical. We therefore tested whether two novel strategies
– overshadowing (Experiment 1) and pre-exposure (Experiment 2) – could inhibit conditioned
nocebo hyperalgesia. Overshadowing involves introducing additional cues during conditioning
that should compete with and overshadow learning about the target nocebo cue. Pre-exposure
involves pre-exposing the target nocebo cue in the absence of pain, which should diminish
its ability to become associated with pain later. In both studies, healthy volunteers
(N = 141) received exposure to a series of electrocutaneous pain stimuli with and
without a sham electrode ‘activated’, which they were led to believe was a genuine
hyperalgesic treatment. Nocebo conditioning was achieved by pairing sham activation
with high pain prior to testing at equivalent pain intensity. In both studies, standard
nocebo conditioning led to clear nocebo hyperalgesia relative to natural history controls.
In Experiment 1, there was no evidence that overshadowing attenuated nocebo hyperalgesia.
Importantly, however, Experiment 2 found that pre-exposure successfully attenuated
nocebo hyperalgesia with post hoc analysis suggesting that this effect was dose-dependent.
These findings provide novel evidence that pre-exposure, but not overshadowing, could
be a cheap and effective way for mitigating the substantial harm caused by conditioned
nocebo hyperalgesia in clinical settings.
Perspective
Nocebo hyperalgesia causes substantial patient burden with few preventive options
available. Our study found novel evidence that pre-exposing treatment cues without
pain, but not overshadowing them with other cues, has the capacity to inhibit conditioned
nocebo hyperalgesia. Pre-exposure may therefore be an effective preventive strategy
to combat nocebo hyperalgesia.
Key Words
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Article info
Publication history
Published online: February 23, 2021
Accepted:
February 11,
2021
Received in revised form:
November 24,
2020
Received:
September 13,
2020
Footnotes
Disclosures: This research was supported by the Australian Research Council (DP180102061). The authors have no conflicts of interest to disclose.
Identification
Copyright
© 2021 by United States Association for the Study of Pain, Inc.
