Reliability of Measuring Conditioned Pain Modulation With the Nociceptive Withdrawal Reflex

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Device: Conditioned Pain Modulation; Device: Conditioned Pain Modulation

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 Type: Interventional
• Enrollment (Actual): 39
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Dep. of Anesthesiology and Pain Medicine, Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Reliability; The same testing procedure is repeated after a delay of 7 days to test the reliability of the measure	Device: Conditioned Pain Modulation; Measure of the conditioned pain modulation with the nociceptive withdrawal reflex and ice water stimulation; Device: Conditioned Pain Modulation; Suprathreshold electrical stimulation with 1.5 times the mean electrical pain detection threshold

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reliability of CPM with the nociceptive withdrawal reflex	two minutes after the cold pressor test

Secondary Outcome Measures

Outcome Measure	Time Frame
Reliability of CPM with electric pain detection threshold	two minutes after the cold pressor test
Reliability of CPM with suprathreshold electrical pain detection threshold stimulation	two minutes after the cold pressor test

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: Aalborg University
• Investigators: Study Director: Michele Curatolo, MD, University Hosptial Bern

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: July 5, 2012
• First Submitted That Met QC Criteria: July 5, 2012
• First Posted (Estimate): July 10, 2012

Study Record Updates

• Last Update Posted (Estimate): January 21, 2013
• Last Update Submitted That Met QC Criteria: January 18, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Conditioned Pain Modulation
• Other Study ID Numbers: 070/12; SNF: SPUM 33CM30_124117