Reliability of Measuring Conditioned Pain Modulation With the Nociceptive Withdrawal Reflex

NCT ID: NCT01636440

Last Updated: 2013-01-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2012-08-31

Brief 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 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.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Reliability

The same testing procedure is repeated after a delay of 7 days to test the reliability of the measure

Group Type: OTHER

Conditioned Pain Modulation

Intervention Type: DEVICE

Measure of the conditioned pain modulation with the nociceptive withdrawal reflex and ice water stimulation

Conditioned Pain Modulation

Intervention Type: DEVICE

Suprathreshold electrical stimulation with 1.5 times the mean electrical pain detection threshold

Interventions

Conditioned Pain Modulation

Measure of the conditioned pain modulation with the nociceptive withdrawal reflex and ice water stimulation

Intervention Type: DEVICE

Conditioned Pain Modulation

Suprathreshold electrical stimulation with 1.5 times the mean electrical pain detection threshold

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Male Gender
• Age 18-65
• Signed Informed Consent

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Aalborg University

OTHER

Sponsor Role: collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michele Curatolo, MD

Role: STUDY_DIRECTOR

University Hosptial Bern

Locations

Dep. of Anesthesiology and Pain Medicine, Bern University Hospital

Bern, , Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 24950186 (View on PubMed)

Other Identifiers

SNF: SPUM 33CM30_124117

Identifier Type: -

Identifier Source: secondary_id

070/12

Identifier Type: -

Identifier Source: org_study_id