Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

Main outcome variable for nocebo responses:

- 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 evocation phase.

Note: A significant difference will be assessed using a Repeated Measures ANOVA as a manipulation check. Then, calculated difference scores represent the magnitude of induced nocebo hyperalgesia and will be used for the primary and first and second secondary hypotheses.

Definitions of other outcome variables:

- The magnitude of nocebo responses (and nocebo-augmented pain) during the evocation phase is defined in the specific nocebo evocation trials that show heightened pain relative to the preceding control trials, for each subject. For EEG analyses, all trials that show the experience of heightened pain in nocebo trials relative to the preceding control trials, during the evocation phase will be used.

Note: Calculated difference scores between the specific nocebo evocation trials that show heightened pain relative to control trials will be used in further analyses of EEG data. While the entirety of the evocation data will be reported and analyzed, the main EEG analyses will include a selection of evocation trials where nocebo responses were reported. It is necessary to use EEG data for trials that show a nocebo response in order to explore electrophysiological correlates of nocebo effects.

0. Manipulation checks: Induction of nocebo hyperalgesia First, the investigators will examine whether significant nocebo hyperalgesia was induced. A Repeated-Measures Analysis of Variance (RM ANOVA) will be performed for nocebo responses (on the pain Numeric Rating Scale), with trial type as the within-subjects factor with two levels (first nocebo evocation trial, first control evocation trial). First evocation trial pairs were chosen based on the clearest effects being observed during piloting and in previous nocebo studies.

1. Primary hypothesis:

Pre-induction to post-induction decreases in resting-state alpha band power will positively correlate with the magnitude of induced nocebo hyperalgesia.

2. Secondary hypotheses:

2.1. The magnitude of induced nocebo hyperalgesia in all nocebo-response evocation trials, will be related to temporal (e.g., Detrended Fluctuation Analysis) and spectral (e.g., Absolute Power, Relative Power and Central Frequency) biomarker values of alpha, beta, and gamma oscillations.

2.2. The experience of nocebo-augmented pain in nocebo trials and pain during control trials of the evocation phase will be characterized by divergent alpha, beta, and gamma oscillation power and peak frequencies.

2.3. The experience of nocebo-augmented pain in nocebo evocation trials and baseline high-pain stimulations, will be characterized by divergent alpha oscillation power and peak frequencies.

2.4. The experience of control and nocebo trials during the induction phase, will be characterized by divergent alpha, beta, and gamma oscillation power and peak frequencies.

2.5. Nocebo induction trials will be characterized by increased gamma band coherence relative to control induction trials during anticipation.

3. Questionnaires To assess the influence of psychological and personality traits, questionnaires will also be included. These will include the Pain Catastrophizing Scale (PSC), the Fear of Pain Questionnaire-III (FPQ-III), the Experience of Cognitive Intrusion of Pain (ECIP) scale, and the Amsterdam Resting State Questionnaire (ARSQ 2.0).

3.1. Correlation analyses will be performed between scores on the questionnaires and the magnitude of the nocebo effect.

3.2. Correlation analyses will be performed between scores on the questionnaires and measures of EEG, as well as pre-to post resting-state differences, in alpha, beta, and gamma frequency bands. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04199858
Study type Interventional
Source Leiden University Medical Center
Contact
Status Completed
Phase N/A
Start date October 21, 2019
Completion date January 7, 2020

See also
  Status Clinical Trial Phase
Completed NCT01659073 - Using Perfusion MRI to Measure the Dynamic Changes in Neural Activation Associated With Caloric Vestibular Stimulation N/A
Recruiting NCT05914311 - Use of Dermabond in Mitigation of Spinal Cord Stimulation (SCS) Trial Lead Migration N/A
Recruiting NCT05422456 - The Turkish Version of Functional Disability Inventory
Enrolling by invitation NCT05422443 - The Turkish Version of Pain Coping Questionnaire
Completed NCT05057988 - Virtual Empowered Relief for Chronic Pain N/A
Completed NCT04385030 - Neurostimulation and Mirror Therapy in Traumatic Brachial Plexus Injury N/A
Recruiting NCT06206252 - Can Medical Cannabis Affect Opioid Use?
Completed NCT05103319 - Simultaneous Application of Ketamine and Lidocaine During an Ambulatory Infusion Therapy as a Treatment Option in Refractory Chronic Pain Conditions
Completed NCT03687762 - Back on Track to Healthy Living Study N/A
Completed NCT04171336 - Animal-assisted Therapy for Children and Adolescents With Chronic Pain N/A
Completed NCT03179475 - Targin® for Chronic Pain Management in Patients With Spinal Cord Injury Phase 4
Completed NCT03418129 - Neuromodulatory Treatments for Pain Management in TBI N/A
Completed NCT03268551 - MEMO-Medical Marijuana and Opioids Study
Recruiting NCT06204627 - TDCS* and Laterality Trainnning in Patients With Chronic Neck Pain N/A
Recruiting NCT06060028 - The Power of Touch. Non-Invasive C-Tactile Stimulation for Chronic Osteoarthritis Pain N/A
Completed NCT05496205 - A SAD Study to Evaluate the Safety, Tolerability and PK/PD of iN1011-N17 in Healthy Volunteers Phase 1
Completed NCT00983385 - Evaluation of Effectiveness and Tolerability of Tapentadol Hydrochloride in Subjects With Severe Chronic Low Back Pain Taking Either WHO Step I or Step II Analgesics or no Regular Analgesics Phase 3
Recruiting NCT05118204 - Randomized Trial of Buprenorphine Microdose Inductions During Hospitalization Phase 4
Terminated NCT03538444 - Repetitive Transcranial Magnetic Stimulation for Opiate Use Disorder N/A
Not yet recruiting NCT05812703 - Biometrics and Self-reported Health Changes in Adults Receiving Behavioral Treatments for Chronic Pain