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Completed

NCT Number: NCT04296968

Sensory Evidence and Expectations in Pain Processing

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.

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Neurology, Klinikum rechts der Isar, Technische Universität München

Munich, Bavaria, 81675, Germany

About this study

Not needed

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Painful stimulation using a laser device (DEKA Stimul 1340, Calenzano, Italy)

Device

In the experimental paradigm, 160 painful stimuli of two intensities (3 J, 3.5 J) will be applied to the dorsum of the left hand using the laser device listed above.

Visual cueing

Device

Preceding to each painful stimulus, visual cues (e.g., blue dot and yellow square) will be presented on a screen indicating the intensity of the subsequent stimulus (low and high intensity) with an accuracy of 75%. The contingencies of the visual cues will be explicitly stated to the participants.

Primary outcomes

  1. Verbal pain rating (NRS; 0: 'no pain' to 100: 'maximum tolerable pain')

    Time frame: 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).

  2. Oscillatory and evoked brain responses pre- and post-stimulus

    Time frame: 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 outcomes

  1. SCRs (µS)

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Technical University of Munich

Other

Collaborators

  • German Research Foundation

Registry information

Official study title

The Role of Sensory Evidence and Expectations in the Cerebral Processing of Pain

Important dates

Study start
2020
Primary completion
2020
Study completion
2020
First posted
Mar 5, 2020
Registry last updated
Apr 1, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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