Reliability of Measuring Conditioned Pain Modulation With the Nociceptive Withdrawal Reflex
Condition: Healthy Volunteers
Study type: Interventional

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.
    

Intervention name(s): Conditioned Pain Modulation; Conditioned Pain Modulation
Intervention type(s): Device; Device
Intervention description(s): Measure of the conditioned pain modulation with the nociceptive withdrawal reflex and ice water stimulation; Suprathreshold electrical stimulation with 1.5 times the mean electrical pain detection threshold
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Conditioned Pain Modulation