Reducing Nocebo Effects on Pressure Pain

Pain Clinical Trial

Official title:

Reducing Nocebo Effects on Pressure Pain: open-and Closed-label Counterconditioning and Extinction Compared

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05284383
• Other study ID #: 2020-02-04-A.W.M.Evers-V1-2085
• Status: Completed
• Phase: N/A
• Start date: March 23, 2021
• Est. completion date: April 5, 2022

Study information

• Verified date: August 2022
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: April 5, 2022
• Est. primary completion date: April 5, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Aged 18-35 years

• Good understanding of written and spoken Dutch or English

Exclusion Criteria:

• Severe somatic or psychiatric morbidity (e.g., heart/lung diseases, DSM-V psychiatric disorders)

• Raynaud's disease, chronic pain complaints at present or in the past

• Current pain complaints (> 2 on NRS)

• Current use of medication (except for birth-control pill)

• Injuries on the non-dominant hand

• Refusal/inability to remove nail polish or artificial nails for the experiment

• Pregnancy or breastfeeding

Related Conditions & MeSH terms

• Hyperalgesia
• Pain

Intervention

Behavioral:
• Closed-label nocebo conditioning
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).
• Closed-label counterconditioning
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).
• Open-label counterconditioning
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).
• Closed-label extinction
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).

Locations

Country	Name	City	State
Netherlands	Leiden University	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Leiden University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nocebo reduction; group comparison	The change in nocebo effects from after nocebo conditioning (part 1) to after either form of counterconditioning or extinction (part 2) will be compared between groups. The nocebo effect is defined as the difference between the pain scored during experimental trials (on a 0-10 NRS) and during control trials (same NRS). The change is calculated by subtracting the nocebo effect after counterconditioning from the nocebo effect after nocebo conditioning.	On the testing day; testing phase of nocebo induction and reduction
Secondary	Nocebo reduction	For all three groups separately, it will be tested whether the nocebo effect is significantly reduced from test phase of nocebo conditioning to the test phase of either form of counterconditioning or extinction. The nocebo effect is defined as the difference between the pain scored during experimental trials (on a 0-10 NRS) and during control trials (same NRS). Nocebo reduction is calculated by subtracting the nocebo effect after counterconditioning from the nocebo effect after nocebo conditioning. For all groups separately, the amount of reduction will be compared to test value 0.	On the testing day; testing phase of nocebo induction and reduction
Secondary	Nocebo reduction; equivalence of the two forms of counterconditioning	It will be tested whether the change in nocebo effects from the test phase of conditioning to the test phase of counterconditioning in the open- and closed-label groups is comparable. The nocebo effect is defined as the difference between the pain scored during experimental trials (on 0-10 NRS) and during control trials (same NRS). The change is calculated by subtracting the nocebo effects after counterconditioning from the nocebo effect after nocebo conditioning.	On the testing day; testing phase of nocebo induction and reduction