Electrophysiological Correlates of Nocebo Effects on Pain

NCT04199858 | Completed DMC

• 1 other identifier: CEP19-1031/532
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Pain is a nociceptive somatosensory process that can arise as a debilitating and chronic symptom in various diseases or following an injury. How pain is experienced can vary widely within and across individuals, and can be shaped by cognitive processes such as learning. Nocebo effects, negative changes in symptom severity attributed to learned outcome-expectations, demonstrate how learning processes can be detrimental for the experience of pain. Research to date has produced inconclusive findings regarding the electrophysiological correlates on nocebo effects. The few studies that have applied electroencephalography (EEG) in this field have pointed towards a potential involvement of alpha-band activity, but the direction of this involvement remains unclear. For example, an EEG study of conditioned nocebo hyperalgesia found a pre to post increase in resting state alpha band power that was correlated with pain catastrophizing scores and not with the magnitude of the nocebo effect. Later, other studies also found pre to post changes in alpha band power, however, these changes were correlated with the magnitude of nocebo effects and not pain catastrophizing. Given the discrepancy in findings, in this study the investigators plan to primarily investigate whether EEG components predict the magnitude of nocebo responses to thermal-pain stimuli. The investigators will also explore electrophysiological correlates during pain anticipation and whether nocebo responses would be significantly related to spectral and temporal EEG biomarkers. This study will utilize a validated model of instructional and associative learning methods (i.e., negative suggestions and classical conditioning, respectively) to experimentally induce nocebo effects on heat-evoked pain. Developing objective, brain-derived markers for nocebo responses, or the detection of individuals most susceptible to nocebo hyperalgesia, will aid in the comprehensive management of pain. This study is conducted at Leiden University.

Conditions

Chronic Pain Syndrome; Chronic Pain, Psychogenic; Chronic Pain; Hyperalgesia

Keywords

Pain; Nocebo; Hyperalgesia; Electroencephalography; EEG; Conditioning; Learning; Negative suggestions

Outcome Measures

Primary Outcomes (1)

• Magnitude of induced nocebo hyperalgesia

  The magnitude of induced nocebo hyperalgesia is defined as the difference in pain ratings for the first nocebo trial compared to the first control trial of the nocebo block evocation phase. A significant difference here is assessed within the mixed model ANOVA. Then, calculated difference scores represent the magnitude of induced effects and will be used in further analyses of EEG data.

  Through study completion, an average of 3 months

Secondary Outcomes (2)

• Magnitude of nocebo responses during evocation

  Through study completion, an average of 3 months

• Nocebo-augmented pain

  Through study completion, an average of 3 months

Other Outcomes (4)

• Electroencephalography components (EEG power in alpha band)

  Through study completion, an average of 3 months

• Electroencephalography components (EEG power in beta band)

  Through study completion, an average of 3 months

• Electroencephalography components (EEG power in gamma band)

  Through study completion, an average of 3 months

Study Arms (1)

Nocebo induction

EXPERIMENTAL

Conditioning and evocation of a nocebo response to a sham (inert) medication contained in a blue or a brown jar, controlled within subjects.

Behavioral: Baseline pain stimulations; Behavioral: Conditioning; Behavioral: Evocation; Other: Electroencephalography (EEG)

Interventions

Baseline pain stimulations BEHAVIORAL

During baseline pain stimulations, a comparison block will include 6 high- and 2 moderate-pain stimulations.

Nocebo induction

Conditioning BEHAVIORAL

During nocebo induction trials, the conditioned stimulus (i.e., a sham medical gel that can increase pain sensitivity, named "TDA" and contained in either a brown or a blue jar) is paired to unconditioned high-pain stimuli (nocebo trials). Lower 'baseline' pain is paired with no gel application (control trials).

Also known as: Nocebo Induction phase

Nocebo induction

Evocation BEHAVIORAL

During nocebo evocation, lower pain stimulations are administered both after the administration of the conditioned stimulus (i.e., a sham medical gel "TDA") and the control stimulus (no medical gel), in order to evoke nocebo responses to the sham hyperalgesic medication.

Also known as: Nocebo testing phase

Nocebo induction

Electroencephalography (EEG) OTHER

In the single group of participants, EEG recordings will be conducted during baseline, during a first resting-state of 5-minutes, during induction/evocation of nocebo responses, and during a second resting-state of 5-minutes.

Nocebo induction

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Participants whose lived gender is male, will be included as male. Participants whose lived gender is female, will be included as female.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18 - 35 years
• Good understanding of the English language
• Normal or corrected to normal vision

You may not qualify if:

• Ever having experienced serious medical or psychiatric conditions (e.g., heart or lung disease, panic attacks, drug addiction, clinical depression),
• Ever having experienced chronic pain complaints (pain for more than 6 months),
• Having experienced persisting painful health problems in the last 6 months,
• Experiencing acute physical pain (e.g., headache, or having used pain medication on the day of testing,
• Pregnancy or breastfeeding,
• Having recent injuries to the wrists or arms on the day of testing,
• Previous participation in this or similar studies (e.g., using conditioning or thermal pain).
• Having consumed psychotropic medication, recreational drugs, analgesic medication, or more than 3 units of alcohol, in the 24 hours prior to the study appointment.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Universiteit Leiden: collaborator
• VU University of Amsterdam: collaborator

Study Sites (1)

Leiden University

Leiden, South Holland, 2333 AK, Netherlands

Location

MeSH Terms

Conditions

Chronic Pain; Hyperalgesia; Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Somatosensory Disorders; Sensation Disorders; Nervous System Diseases

Study Officials

• Andrea WM Evers, Prof. Dr.

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: A double-blind randomization list was created by an independent researcher to randomize participants into two counterbalanced conditions: participants either receive the nocebo sham medical gel in a blue or in a brown jar. Complete blinding of the researchers during the experiment is not possible due to the nature of conditioning/ suggestion paradigms. Participants are blind with respect to the conditioning/nocebo manipulation.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 9, 2019
• First Posted: December 16, 2019
• Study Start: October 21, 2019
• Primary Completion: January 7, 2020
• Study Completion: January 7, 2020
• Last Updated: January 9, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data will become available immediately after publication of the study and will be retained for 15 years.
• Access Criteria: Data can be shared with scientists in relevant fields for the purpose of future studies such as replication or meta-analysis (or with designated persons for monitoring purposes).

Locations

NL (1)