Sensory Evidence and Expectations in Pain Processing

Not Applicable

Completed

• Conditions: Experimental Pain in Healthy Human Participants

• Registration Number: NCT04296968
• Lead Sponsor: Technical University of Munich

Brief Summary

Pain is a highly complex and subjective phenomenon which is not only rooted in sensory information but also shaped by cognitive processes such as expectation. However, the interaction of brain activity cording sensory information and expectation in pain processing are not completely understood. Predictive coding models postulate specific hypothesis about the interplay between bottom-up sensory information and top-down expectations in terms of prediction errors and predictions, respectively. They further implicate brain oscillations at different frequencies, which play a crucial role in processing prediction errors and predictions. More specifically, recent evidence in visual and auditory modalities suggests that predictions are reflected by alpha (8-13 Hz) and beta oscillations (14-30 Hz) and prediction errors by gamma oscillations (60-100 Hz). However, for the processing of pain, these frequency-specific relationships have not been addressed so far. The current project aims to investigate brain activity which reflects predictions, prediction errors and sensory evidence in pain processing using a cueing paradigm. To this end, we will apply painful stimuli with low and high intensity to the dorsum of the left hand in 50 healthy subjects. A visual cue, preceding to each painful stimulus, will predict the intensity of the consecutive painful stimulus (low vs. high) with a probability of 75%. After each painful stimulus, participants will be asked to rate the perceived pain intensity. Electroencephalography (EEG) and skin conductance will be recorded continuously during anticipation and stimulation intervals. This paradigm enables us to compare pain-associated brain responses of validly and invalidly cued trials, i.e. the representation of the prediction error, on the one hand. On the other hand, brain activity related to predictions can be investigated in the anticipation interval preceding to the painful stimulus by comparing trials with low and high intensity cues. Further, we will compare models including predictions, prediction error and sensory evidence to ascertain the involvement of each brain response in processing sensory information and expectation. Results of the study promise to elucidate the interplay of predictions, predictions errors and sensory evidence in pain processing and how they differentially relate to neural oscillations at different frequency bands and pain-evoked responses.

Detailed Description

Not needed

Study Timeline

• Study Start: 2020-03-01
• Study First Submitted: 2020-03-03
• Study First Submitted QC: 2020-03-03
• Study First Posted: 2020-03-05
• Primary Completion: 2020-12-01
• Study Completion: 2020-12-01
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-30
• Last Update Posted: 2021-04-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Age 18-65 years
• Right-handedness
• Written informed consent

Exclusion Criteria

• Pregnancy
• Neurological or psychiatric diseases (e.g. epilepsy, stroke, depression, anxiety disorders)
• Severe general illnesses (e.g. tumors, diabetes)
• Skin diseases (e.g. dermatitis, psoriasis or eczema)
• Current or recurrent pain
• Regular intake of medication
• Surgical procedures involving the head or spinal cord
• Metal (except titanium) or electronic implants
• Side-effects following previous thermal stimulation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Verbal pain rating (NRS; 0: 'no pain' to 100: 'maximum tolerable pain')	During 40 minutes of the experimental paradigm	160 painful stimuli will be applied to the participants' left hand. Participants will be asked to verbally rate the perceived pain intensity of each stimulus on a numerical rating scale (see above).
Oscillatory and evoked brain responses pre- and post-stimulus	During 40 minutes of the experimental paradigm	EEG including 64 channels will be recorded. In offline analyses, power of oscillatory brain activity will be quantified in the alpha (8-13 Hz), beta (14-30 Hz) and gamma (60-100 Hz) frequency bands. In addition, laser-evoked potentials (LEPs) will be quantified with regard to amplitudes and latencies.

Secondary Outcome Measures

Name	Time	Method
SCRs (µS)	During 40 minutes of the experimental paradigm	SCRs will be recorded using two electrodes attached to the index and middle finger of the left hand.

Trial Locations

Locations (1)

Department of Neurology, Klinikum rechts der Isar, Technische Universität München; 🇩🇪 Munich, Bavaria, Germany