Healthy VolunteersNCT01636440
Reliability of Measuring Conditioned Pain Modulation With the Nociceptive Withdrawal Reflex
A study testing Conditioned Pain Modulation in people with Healthy Volunteers, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial summary
Conditioned pain modulation is the ability of the spine to describe changes in pain perception, if two different painful stimulations take place. The reliability of the conditioned pain modulation has not been studied, the instruments used to measure the conditioned pain modulation are sparse and have proven difficult… Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Conditioned Pain Modulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jun 2012to Aug 2012
- 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
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male Gender
- Age 18-65
- Signed Informed Consent
Who cannot join
- Signs or suspicion of neurologic dysfunction or disease
- Ongoing treatment with any drug known to influence pain modulation: any analgesic, antidepressant, anticonvulsant or benzodiazepine
- Intake of any analgesic drug during the 48h preceding the experiment.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Dep. of Anesthesiology and Pain Medicine, Bern University Hospital
Bern, 3010
About this study
Conditioned pain modulation is the ability of the spine to describe changes in pain perception, if two different painful stimulations take place. The reliability of the conditioned pain modulation has not been studied, the instruments used to measure the conditioned pain modulation are sparse and have proven difficult to use in a well reproductible way. This study is using an existing pain test, relying on the reflex in a muscle after a painful electrical stimulation. We will test 34 healthy volunteers in order to test the reliability of the conditioned pain modulation with the nociceptive withdrawal reflex combined to a ice water test.
Read the detailed description
Background
Chronic pain is characterized by changes in the central processing of sensory inputs. Quantitative sensory tests (QST) explore central excitability in humans and have the potential to detect altered central pain processing in individual patients.
QST were developed to assess the responses to sensory stimuli for research purposes, providing psychophysical and electrophysiological methods for the assessment of the nociceptive system. Reliability is an essential condition for using QST in research and clinical practice. It can be defined as the consistency of measurements across time, patients or observers, and the extent to which it is error-free. Three categories have been assessed for reliability in QST measures: intra-rater, inter-rater and test-retest reliability. Reliability of QST measures in healthy volunteers are encouraging in regard to good repeatability of QST measures over the time in the same subjects. Inter-rater reliability, a prerequisite to compare different measures in between different studies, are also highly encouraging.
Under normal conditions, pain after application of a test nociceptive stimulus is attenuated by the application of an additional "conditioning" noxious stimulus to a remote body region, reflecting diffuse endogenous inhibition. This is defined as conditioned pain modulation (CPM), also known as the "pain inhibits pain" paradigm. CPM has been object of much work in the last years. It goes back to the exploration of endogenous analgesia via descending pain-modulatory systems, which started about three decades ago in animal models. Descending inhibitory pathways are under cerebral control, mediating modulation of pain perception by emotional, motivational and cognitive factors. Alterations of CPM are a known risk factor concerning acute and chronic pain syndromes.
Very few reliability studies on CPM have been conducted to date. To our knowledge, only S. Cathcart et al used occlusion cuff algometry and pressure pain detection to assess the test-retest reliability in healthy volunteers. A study in chronic pain patients from our group has shown great variability in CPM. It is unclear whether this phenomenon is related to high interindividual variability of the CPM measure itself, or to poor reliability. In an analysis of own data extracted from a pharmacological study, CPM measured at three different sessions in patients with low back pain displayed very poor reliability.
The nociceptive withdrawal reflex is an electrophysiological measure. Compared to psychophysical measures which rely on the subject's pain perception, the reflex could be a more reproducible and stable measure over time.
Objective
The primary aim of the present study is to assess the reliability of CPM using the nociceptive withdrawal reflex as test stimulus and the ice water test as conditioning stimulus in 34 consecutive patients, with a 7 days interval between two sessions.
Secondary aim is to compare the reliability of CPM with the nociceptive withdrawal reflex to the reliability of CPM assessed with subjective pain assessments, i.e. pain threshold and pain intensity after electrical stimulation.
Methods
Repeated assessments of CPM using the nociceptive withdrawal reflex threshold, electrical pain detection threshold and suprathreshold electrical stimulation of the skin, with ice-water as conditioning stimuli in all three models. There will be a 7 days interval between two measurements.
- Conditions
- Healthy Volunteers
- Being tested
- Conditioned Pain Modulation
- Keywords
- Conditioned Pain Modulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conditioned Pain ModulationDevice
Measure of the conditioned pain modulation with the nociceptive withdrawal reflex and ice water stimulation
Conditioned Pain ModulationDevice
Suprathreshold electrical stimulation with 1.5 times the mean electrical pain detection threshold
| Study group | Role | What they receive |
|---|---|---|
| Reliability | Other | The same testing procedure is repeated after a delay of 7 days to test the reliability of the measure Receives: Device: Conditioned Pain Modulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reliability of CPM with the nociceptive withdrawal reflex
Measured: two minutes after the cold pressor test
Secondary outcomes (2)
Reliability of CPM with electric pain detection threshold
Measured: two minutes after the cold pressor test
Reliability of CPM with suprathreshold electrical pain detection threshold stimulation
Measured: two minutes after the cold pressor test
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2012 (estimated)
- Study startJun 2012
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- Aalborg University
- Responsible party
- Sponsor
- Investigators
- Michele Curatolo, MD, Study director, University Hosptial Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01636440
- Sponsor's protocol ID
- 070/12
- Other IDs
- SNF: SPUM 33CM30_124117
- Status last verified
- Jan 2013
- First submitted
- 5 Jul 2012
- Last updated
- 21 Jan 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Biurrun Manresa JA, Fritsche R, Vuilleumier PH, Oehler C, Morch CD, Arendt-Nielsen L, Andersen OK, Curatolo M. Is the conditioned pain modulation paradigm reliable? A test-retest assessment using the nociceptive withdrawal reflex. PLoS One. 2014 Jun 20;9(6):e100241. doi: 10.1371/journal.pone.0100241. eCollection 2014.
PubMed 24950186
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reliability of Measuring Conditioned Pain Modulation With the Nociceptive Withdrawal Reflex
- ClinicalTrials.gov ID
- NCT01636440
- Acronym / sponsor ID
- 070/12
- Conditions
- Healthy Volunteers
- Keywords
- Conditioned Pain Modulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- Aalborg University
- Study start
- Jun 2012
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 10 Jul 2012 (estimated)
- 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.
Conditioned pain modulation is the ability of the spine to describe changes in pain perception, if two different painful stimulations take place. The reliability of the conditioned pain modulation has not been studied, the instruments used to measure the conditioned pain modulation are sparse and have proven difficult to use in a well reproductible way. This study is using an existing pain test, relying on the reflex in a muscle after a painful electrical stimulation. We will test 34 healthy volunteers in order to test the reliability of the conditioned pain modulation with the nociceptive withdrawal reflex combined to a ice water test.
Detailed description
Background
Chronic pain is characterized by changes in the central processing of sensory inputs. Quantitative sensory tests (QST) explore central excitability in humans and have the potential to detect altered central pain processing in individual patients.
QST were developed to assess the responses to sensory stimuli for research purposes, providing psychophysical and electrophysiological methods for the assessment of the nociceptive system. Reliability is an essential condition for using QST in research and clinical practice. It can be defined as the consistency of measurements across time, patients or observers, and the extent to which it is error-free. Three categories have been assessed for reliability in QST measures: intra-rater, inter-rater and test-retest reliability. Reliability of QST measures in healthy volunteers are encouraging in regard to good repeatability of QST measures over the time in the same subjects. Inter-rater reliability, a prerequisite to compare different measures in between different studies, are also highly encouraging.
Under normal conditions, pain after application of a test nociceptive stimulus is attenuated by the application of an additional "conditioning" noxious stimulus to a remote body region, reflecting diffuse endogenous inhibition. This is defined as conditioned pain modulation (CPM), also known as the "pain inhibits pain" paradigm. CPM has been object of much work in the last years. It goes back to the exploration of endogenous analgesia via descending pain-modulatory systems, which started about three decades ago in animal models. Descending inhibitory pathways are under cerebral control, mediating modulation of pain perception by emotional, motivational and cognitive factors. Alterations of CPM are a known risk factor concerning acute and chronic pain syndromes.
Very few reliability studies on CPM have been conducted to date. To our knowledge, only S. Cathcart et al used occlusion cuff algometry and pressure pain detection to assess the test-retest reliability in healthy volunteers. A study in chronic pain patients from our group has shown great variability in CPM. It is unclear whether this phenomenon is related to high interindividual variability of the CPM measure itself, or to poor reliability. In an analysis of own data extracted from a pharmacological study, CPM measured at three different sessions in patients with low back pain displayed very poor reliability.
The nociceptive withdrawal reflex is an electrophysiological measure. Compared to psychophysical measures which rely on the subject's pain perception, the reflex could be a more reproducible and stable measure over time.
Objective
The primary aim of the present study is to assess the reliability of CPM using the nociceptive withdrawal reflex as test stimulus and the ice water test as conditioning stimulus in 34 consecutive patients, with a 7 days interval between two sessions.
Secondary aim is to compare the reliability of CPM with the nociceptive withdrawal reflex to the reliability of CPM assessed with subjective pain assessments, i.e. pain threshold and pain intensity after electrical stimulation.
Methods
Repeated assessments of CPM using the nociceptive withdrawal reflex threshold, electrical pain detection threshold and suprathreshold electrical stimulation of the skin, with ice-water as conditioning stimuli in all three models. There will be a 7 days interval between two measurements.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Reliability | Other | Device: Conditioned Pain ModulationThe same testing procedure is repeated after a delay of 7 days to test the reliability of the measure |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male Gender
- Age 18-65
- Signed Informed Consent
Key exclusion criteria (3 listed)
- Signs or suspicion of neurologic dysfunction or disease
- Ongoing treatment with any drug known to influence pain modulation: any analgesic, antidepressant, anticonvulsant or benzodiazepine
- Intake of any analgesic drug during the 48h preceding the experiment.
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 |
|---|---|---|
| Conditioned Pain ModulationMeasure of the conditioned pain modulation with the nociceptive withdrawal reflex and ice water stimulation | Device | Reliability |
| Conditioned Pain ModulationSuprathreshold electrical stimulation with 1.5 times the mean electrical pain detection threshold | Device | Reliability |
Primary outcome
Reliability of CPM with the nociceptive withdrawal reflex
Time frame: two minutes after the cold pressor test
2 secondary outcomes
Reliability of CPM with electric pain detection threshold
Time frame: two minutes after the cold pressor test
Reliability of CPM with suprathreshold electrical pain detection threshold stimulation
Time frame: two minutes after the cold pressor test
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 21 Jan 2013.
- Derived from this study: PubMed 24950186Biurrun Manresa JA, Fritsche R, Vuilleumier PH, Oehler C, Morch CD, Arendt-Nielsen L, Andersen OK, Curatolo M. Is the conditioned pain modulation paradigm reliable? A test-retest assessment using the nociceptive withdrawal reflex. PLoS One. 2014 Jun 20;9(6):e100241. doi: 10.1371/journal.pone.0100241. eCollection 2014.
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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.
Michele Curatolo, MD study director
University Hosptial Bern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Conditioned Pain Modulation in people with Healthy Volunteers, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
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 3 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 21 Jan 2013. 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 Switzerland. 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?
Reliability of CPM with the nociceptive withdrawal reflex (time frame: two minutes after the cold pressor test). 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 NCT01636440, which also lists 1 linked publication.
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 21 Jan 2013; AzTrials last refreshed its copy on 7 Nov 2026.