Reducing Nocebo Effects on Pressure Pain
Condition: Pain; Hyperalgesia
MeSH terms: Hyperalgesia
Study type: Interventional

Summary: 
      Nocebo effects are known to adversely affect the experience of various physical symptoms,
      such as pain and itch. Nocebo effects can be induced by associative learning mechanisms of
      classical conditioning. Furthermore, recent studies have shown that counterconditioning can
      successfully reduce nocebo effects, and to a larger extent than mere extinction, which
      suggests counterconditioning can be an innovative method for desensitization of symptoms.
      When using such procedures in clinical practice, deception of patients should be avoided as
      much as possible. The use of open-label procedures could provide a promising alternative.
      While previous studies have already shown that open-label placebos are effective, the effects
      of open-label counterconditioning and closed-label counterconditioning are not extensively
      investigated in comparison to other strategies, such as extinction, and not yet compared
      amongst each other. Before implementing such a procedure in clinical practice, it would be
      relevant to get an insight in the efficacy of both open- and closed-label counterconditioning
      in healthy participants as compared to extinction and to investigate whether open-label
      counterconditioning can be equally effective as closed-label counterconditioning.
      Furthermore, it would be relevant to study the induction and reduction of nocebo effects
      using a pain modality that mimics the type of pain that people suffering from several chronic
      pain conditions experience, such as pressure pain. The main aim of the current study is to
      investigate whether open- and closed-label counterconditioning are more effective in reducing
      nocebo effects than extinction. To this aim, it will be investigated whether open- and
      closed-label counterconditioning lead to stronger reductions in nocebo effects on pressure
      pain than (closed-label) extinction, and whether all three successfully reduce nocebo
      effects. Finally, it will be tested whether open- and closed label counterconditioning are
      comparable in effectivity.
    

Detailed description: 
      The primary objective of the study is to investigate whether open- and closed-label
      counterconditioning are more effective in reducing nocebo effects than extinction.

      The experimental (open- and closed-label counterconditioning) and control (extinction) groups
      will be compared on the change in the nocebo effect from before to after counterconditioning.
      The nocebo effect is defined as the mean difference in self-reported pain ratings (on a
      numeric rating scale from 0 (no pain) to 10 (worst pain imaginable))during all experimental
      trials and control trials in the test phase of nocebo conditioning and the test phase of
      counterconditioning/extinction. The reduction of the nocebo effect will be determined by
      calculating the mean difference between the nocebo effect after conditioning and after
      counterconditioning/extinction. It is expected that participants in both counterconditioning
      groups will show a larger reduction of the nocebo effect than participants in the extinction
      group. A one-way ANOVA will be conducted, to examine the main effect of group on the amount
      of change in nocebo effects. Then, post-hoc analyses will be conducted after the primary
      analysis, to test for differences between the three forms of nocebo reduction.

      Secondary, it will be tested whether all three procedures (open- and closed-label
      counterconditioning and extinction) lead to a significant reduction of the nocebo effect, by
      comparing the amount of reduction to test value 0. It is hypothesized that all groups show a
      significant reduction.

      Finally, it will be investigated whether open- and closed-label counterconditioning
      procedures are comparable in terms of their ability to reduce nocebo effects on pressure
      pain. Both groups are expected to be comparable in efficacy of reducing the nocebo effect.
    

Intervention name(s): Closed-label nocebo conditioning; Closed-label counterconditioning; Open-label counterconditioning; Closed-label extinction
Intervention type(s): Behavioral; Behavioral; Behavioral; Behavioral
Intervention description(s): Conditioning consists of a learning and test phase. In the learning phase, a message indicating the sham activation of a Transcutaneous Electrical Nerve Stimulation (TENS) device (CS) will be repeatedly paired with a moderate intensity pressure pain stimulus, whereas a message indicating the deactivation of the sham device will be repeatedly paired with a slightly painful pressure pain stimulus. Participants will be given a verbal suggestion in line with the conditioning procedure (i.e. activation of the device will increase their pain). The testing phase is similar to the learning phase, but a slight pressure pain intensity is used for all trials, to test for a nocebo effect (i.e. to test whether participants score "TENS on" trials as more painful than "TENS off" trials).; Counterconditioning consists of a learning and test phase. In the learning phase, a message indicating the sham activation of the TENS device (CS) is now repeatedly paired with a non-painful intensity pressure pain stimulus, whereas a message indicating the sham deactivation of the TENS device will be repeatedly paired with a slightly painful pressure pain stimulus. Participants will be given a verbal suggestion in line with the counterconditioning procedure (i.e. activation of the device will reduce their pain). The testing phase is similar to the learning phase, but a slight pressure pain intensity is used for all trials, to test whether the nocebo effect is successfully reduced (i.e. to test whether participants no longer score "TENS on" trials as more painful than "TENS off" trials or even score "TENS on" trials as less painful).; Counterconditioning consists of a learning and test phase. In the learning phase, a message indicating the sham activation of the TENS device (CS) is now repeatedly paired with a non-painful intensity pressure pain stimulus, whereas a message indicating the sham deactivation of the TENS device will be repeatedly paired with a slightly painful pressure pain stimulus. Participants will be given a open-label verbal suggestions in line with the counterconditioning procedure (i.e. they are told counterconditioning will be used to reduce nocebo effects and they are told the device is sham, but that their pain will still be influenced because of the placebo effect). The testing phase is similar to the learning phase, but a slight pressure pain intensity is used for all trials, to test whether the nocebo effect is successfully reduced (i.e. to test whether participants no longer score "TENS on" trials as more painful than "TENS off" trials or even score "TENS on" trials as less painful).; Extinction consists of a learning and test phase. In the learning phase, slightly painful stimuli are used for all trials. During the testing phase, again a slight pressure pain intensity is used for all trials, to test whether the nocebo effect is successfully reduced (i.e. to test whether participants no longer score "TENS on" trials as more painful than "TENS off" trials).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Pressure pain; Nocebo effect; Conditioning; Counterconditioning