Reliability of Measuring Conditioned Pain Modulation With the Nociceptive Withdrawal Reflex

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.

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.