Stimulus-Preceding Negativity and Nocebo Effects in Pain: An EEG Study

The nocebo effect, which occurs when an inert intervention results in the worsening of symptoms due to negative expectations, affects the experience of pain. Negative expectations may be shaped through verbal suggestions and classical conditioning, but it is unclear how these learning processes affect anticipatory brain processing related to nocebo-enhanced pain. Therefore, this within-subjects study explored whether stimulus-preceding negativity (SPN), a slow-wave event-related potential component that reflects perceptual and emotional anticipation, would increase in response to cues that predicted high heat pain compared to cues that predicted moderate heat pain. A positive relationship between SPN amplitude and the nocebo effect was expected during evocation. The sample consisted of 36 healthy adults (24 females). SPN was measured from -500 ms to 0 ms relative to pain stimulus onset using electroencephalography, and pain intensity was measured using a numeric rating scale. A...Show moreThe nocebo effect, which occurs when an inert intervention results in the worsening of symptoms due to negative expectations, affects the experience of pain. Negative expectations may be shaped through verbal suggestions and classical conditioning, but it is unclear how these learning processes affect anticipatory brain processing related to nocebo-enhanced pain. Therefore, this within-subjects study explored whether stimulus-preceding negativity (SPN), a slow-wave event-related potential component that reflects perceptual and emotional anticipation, would increase in response to cues that predicted high heat pain compared to cues that predicted moderate heat pain. A positive relationship between SPN amplitude and the nocebo effect was expected during evocation. The sample consisted of 36 healthy adults (24 females). SPN was measured from -500 ms to 0 ms relative to pain stimulus onset using electroencephalography, and pain intensity was measured using a numeric rating scale. A nocebo effect was induced through a negative verbal suggestion and classical conditioning. During induction participants learned to associate the sham activation of a Transcutaneous Electrical Nerve Stimulation device with high pain stimuli (nocebo), relative to moderate intensity stimuli when the device was turned off (control). During evocation only moderate pain was applied. Results showed a significant nocebo effect, p < .001. There was no difference in SPN amplitude between nocebo and control trials in the evocation phase, p = .26. There was a trend towards greater negativity for nocebo trials. There was no relationship between SPN and the nocebo effect during evocation, p = .41. Post-hoc, there was a positive relationship between SPN and pain ratings, p = .002. These results suggest that SPN does not directly reflect anticipatory processing related to nocebo-enhanced pain, but that it does become larger as an individual experiences more intense pain. This finding is clinically relevant because it argues that the estimation of SPN could perhaps aid in the assessment and treatment of pain. Future research should explore SPN further with the use of standardized experimental designs and multiple levels of pain intensity, and with the inclusion of clinical groups.Show less

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Stimulus-Preceding Negativity and Nocebo Effects in Pain: An EEG Study