Experimental Pain in Healthy Human ParticipantsNCT04296968
Sensory Evidence and Expectations in Pain Processing
A study testing Painful stimulation using a laser device (DEKA Stimul 1340, Calenzano, Italy) and Visual cueing in people with Experimental Pain in Healthy Human Participants, run by Technical University of Munich at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Experimental Pain in Healthy Human Participants
- What is being tested?
- Painful stimulation using a laser device (DEKA Stimul 1340, Calenzano, Italy) and Visual cueing
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteGermany
- Study dates
- 1 Mar 2020to 1 Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18-65 years
- Right-handedness
- Written informed consent
Who cannot join
- 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
Show all 9Show fewer
- Surgical procedures involving the head or spinal cord
- Metal (except titanium) or electronic implants
- Side-effects following previous thermal stimulation
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Neurology, Klinikum rechts der Isar, Technische Universität München
Munich, Bavaria, 81675
About this study
Official title: The Role of Sensory Evidence and Expectations in the Cerebral Processing of Pain
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.
Read the detailed description
Not needed
- Being tested
- Painful stimulation using a laser device (DEKA Stimul 1340, Calenzano, Italy), Visual cueing
- Keywords
- pain, electroencephalography, laser-evoked potentials, neural oscillations, brain, predictive coding
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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 cueingDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Expectation and experimental pain in humans | Experimental | Not described Receives: Device: Painful stimulation using a laser device (DEKA Stimul 1340, Calenzano, Italy); Device: Visual cueing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Verbal pain rating (NRS; 0: 'no pain' to 100: 'maximum tolerable pain')
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).
Measured: During 40 minutes of the experimental paradigm
Oscillatory and evoked brain responses pre- and post-stimulus
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.
Measured: During 40 minutes of the experimental paradigm
Secondary outcomes (1)
SCRs (µS)
SCRs will be recorded using two electrodes attached to the index and middle finger of the left hand.
Measured: During 40 minutes of the experimental paradigm
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2020
- Study start1 Mar 2020
- Primary completion1 Dec 2020
- Study completion1 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Experimental Pain in Healthy Human ParticipantsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Each participant will participate in one experimental session with a duration of 40 minutes. The experimental paradigm consists of 160 painful stimuli of two intensities (low and high), which will be applied using a laser stimulation device (DEKA Stimul 1340, Calenzano, Italy). Preceding to each painful stimulus, visual cues will be presented indicating the intensity of the subsequent stimulus with an accuracy of 75%. After each painful stimulus, participants will be prompted to verbally rate the pain intensity on a scale ranging from 0 ('no pain') to 100 ('maximum tolerable pain'). Brain activity and autonomic activity will be recorded simultaneously using EEG and skin conductance responses (SCRs), respectively.
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Technical University of Munich
- Sponsor type
- University, hospital or other
- Collaborators
- German Research Foundation
- Responsible party
- Principal investigator, Markus Ploner, Technical University of Munich
- Investigators
- Markus Ploner, Prof Dr med, Principal investigator, Department of Neurology, Klinikum rechts der Isar, TUM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04296968
- Sponsor's protocol ID
- 03/2020
- Status last verified
- Mar 2021
- First submitted
- 3 Mar 2020
- Last updated
- 1 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pseudonymized individual participant data sets will be made available at the OSF online repository \[https://osf.io/\] upon publication.
Publications
Bastos AM, Usrey WM, Adams RA, Mangun GR, Fries P, Friston KJ. Canonical microcircuits for predictive coding. Neuron. 2012 Nov 21;76(4):695-711. doi: 10.1016/j.neuron.2012.10.038.
PubMed 23177956Bastos AM, Vezoli J, Bosman CA, Schoffelen JM, Oostenveld R, Dowdall JR, De Weerd P, Kennedy H, Fries P. Visual areas exert feedforward and feedback influences through distinct frequency channels. Neuron. 2015 Jan 21;85(2):390-401. doi: 10.1016/j.neuron.2014.12.018. Epub 2014 Dec 31.
PubMed 25556836Buchel C, Geuter S, Sprenger C, Eippert F. Placebo analgesia: a predictive coding perspective. Neuron. 2014 Mar 19;81(6):1223-1239. doi: 10.1016/j.neuron.2014.02.042.
PubMed 24656247de Lange FP, Heilbron M, Kok P. How Do Expectations Shape Perception? Trends Cogn Sci. 2018 Sep;22(9):764-779. doi: 10.1016/j.tics.2018.06.002. Epub 2018 Jun 29.
PubMed 30122170Egner T, Monti JM, Summerfield C. Expectation and surprise determine neural population responses in the ventral visual stream. J Neurosci. 2010 Dec 8;30(49):16601-8. doi: 10.1523/JNEUROSCI.2770-10.2010.
PubMed 21147999Fazeli S, Buchel C. Pain-Related Expectation and Prediction Error Signals in the Anterior Insula Are Not Related to Aversiveness. J Neurosci. 2018 Jul 18;38(29):6461-6474. doi: 10.1523/JNEUROSCI.0671-18.2018. Epub 2018 Jun 22.
PubMed 29934355Geuter S, Boll S, Eippert F, Buchel C. Functional dissociation of stimulus intensity encoding and predictive coding of pain in the insula. Elife. 2017 May 19;6:e24770. doi: 10.7554/eLife.24770.
PubMed 28524817Todorovic A, de Lange FP. Repetition suppression and expectation suppression are dissociable in time in early auditory evoked fields. J Neurosci. 2012 Sep 26;32(39):13389-95. doi: 10.1523/JNEUROSCI.2227-12.2012.
PubMed 23015429Todorovic A, van Ede F, Maris E, de Lange FP. Prior expectation mediates neural adaptation to repeated sounds in the auditory cortex: an MEG study. J Neurosci. 2011 Jun 22;31(25):9118-23. doi: 10.1523/JNEUROSCI.1425-11.2011.
PubMed 21697363
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Sensory Evidence and Expectations in the Cerebral Processing of Pain
- ClinicalTrials.gov ID
- NCT04296968
- Acronym / sponsor ID
- 03/2020
- Keywords
- pain, electroencephalography, laser-evoked potentials, neural oscillations, brain, predictive coding
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Technical University of MunichUniversity, hospital or other
- Collaborators
- German Research Foundation
- Study start
- 1 Mar 2020 (actual)
- Primary completion
- 1 Dec 2020 (actual)
- Study completion
- 1 Dec 2020 (actual)
- First posted
- 5 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Each participant will participate in one experimental session with a duration of 40 minutes. The experimental paradigm consists of 160 painful stimuli of two intensities (low and high), which will be applied using a laser stimulation device (DEKA Stimul 1340, Calenzano, Italy). Preceding to each painful stimulus, visual cues will be presented indicating the intensity of the subsequent stimulus with an accuracy of 75%. After each painful stimulus, participants will be prompted to verbally rate the pain intensity on a scale ranging from 0 ('no pain') to 100 ('maximum tolerable pain'). Brain activity and autonomic activity will be recorded simultaneously using EEG and skin conductance responses (SCRs), respectively.
| Arm | Type | Receives |
|---|---|---|
| Expectation and experimental pain in humans | Experimental | Device: Painful stimulation using a laser device (DEKA Stimul 1340, Calenzano, Italy), Device: Visual cueing |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 18-65 years
- Right-handedness
- Written informed consent
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Painful stimulation using a laser device (DEKA Stimul 1340, Calenzano, Italy)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. | Device | Expectation and experimental pain in humans |
| Visual cueingPreceding 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. | Device | Expectation and experimental pain in humans |
Primary outcome
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).
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.
1 secondary outcome
SCRs (µS)
Time frame: During 40 minutes of the experimental paradigm
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2021.
- Background: PubMed 23177956Bastos AM, Usrey WM, Adams RA, Mangun GR, Fries P, Friston KJ. Canonical microcircuits for predictive coding. Neuron. 2012 Nov 21;76(4):695-711. doi: 10.1016/j.neuron.2012.10.038.
- Background: PubMed 25556836Bastos AM, Vezoli J, Bosman CA, Schoffelen JM, Oostenveld R, Dowdall JR, De Weerd P, Kennedy H, Fries P. Visual areas exert feedforward and feedback influences through distinct frequency channels. Neuron. 2015 Jan 21;85(2):390-401. doi: 10.1016/j.neuron.2014.12.018. Epub 2014 Dec 31.
- Background: PubMed 24656247Buchel C, Geuter S, Sprenger C, Eippert F. Placebo analgesia: a predictive coding perspective. Neuron. 2014 Mar 19;81(6):1223-1239. doi: 10.1016/j.neuron.2014.02.042.
- Background: PubMed 30122170de Lange FP, Heilbron M, Kok P. How Do Expectations Shape Perception? Trends Cogn Sci. 2018 Sep;22(9):764-779. doi: 10.1016/j.tics.2018.06.002. Epub 2018 Jun 29.
- Background: PubMed 21147999Egner T, Monti JM, Summerfield C. Expectation and surprise determine neural population responses in the ventral visual stream. J Neurosci. 2010 Dec 8;30(49):16601-8. doi: 10.1523/JNEUROSCI.2770-10.2010.
- Background: PubMed 29934355Fazeli S, Buchel C. Pain-Related Expectation and Prediction Error Signals in the Anterior Insula Are Not Related to Aversiveness. J Neurosci. 2018 Jul 18;38(29):6461-6474. doi: 10.1523/JNEUROSCI.0671-18.2018. Epub 2018 Jun 22.
- Background: PubMed 28524817Geuter S, Boll S, Eippert F, Buchel C. Functional dissociation of stimulus intensity encoding and predictive coding of pain in the insula. Elife. 2017 May 19;6:e24770. doi: 10.7554/eLife.24770.
- Background: PubMed 23015429Todorovic A, de Lange FP. Repetition suppression and expectation suppression are dissociable in time in early auditory evoked fields. J Neurosci. 2012 Sep 26;32(39):13389-95. doi: 10.1523/JNEUROSCI.2227-12.2012.
- Background: PubMed 21697363Todorovic A, van Ede F, Maris E, de Lange FP. Prior expectation mediates neural adaptation to repeated sounds in the auditory cortex: an MEG study. J Neurosci. 2011 Jun 22;31(25):9118-23. doi: 10.1523/JNEUROSCI.1425-11.2011.
- Individual participant dataSharing planned: Yes. Pseudonymized individual participant data sets will be made available at the OSF online repository [https://osf.io/] upon publication.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Markus Ploner, Prof Dr med principal investigator
Department of Neurology, Klinikum rechts der Isar, TUM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Painful stimulation using a laser device (DEKA Stimul 1340, Calenzano, Italy) and Visual cueing in people with Experimental Pain in Healthy Human Participants, run by Technical University of Munich at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Verbal pain rating (NRS; 0: 'no pain' to 100: 'maximum tolerable pain') (time frame: During 40 minutes of the experimental paradigm). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04296968, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2021.