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A Protocol of Manual Tests to Measure Sensation and Pain in Humans
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Conditioned Pain Modulation Inter-Site Variability Study: Effect Sizes and Test-Retest Reliability of Two Models.

Yi-Wun Lin1,2, Hannah Schmidt1,3, Niko Möller-Grell1,3

  • 1Department of Neurophysiology, Mannheim Center of Translational Neuroscience (MCTN), Ruprecht Karls University Heidelberg, Mannheim, Germany.

European Journal of Pain (London, England)
|May 4, 2026
PubMed
Summary
This summary is machine-generated.

Optimizing conditioned pain modulation (CPM) protocols is key for chronic pain assessment. Testing pressure pain thresholds after cold water immersion shows promise for reliable, individualized clinical evaluation of descending pain inhibition.

Keywords:
conditioned pain modulationheat pain sensitivitypressure pain thresholdreference datatest–retest reliability

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Area of Science:

  • Neuroscience
  • Pain Research
  • Psychophysics

Background:

  • Conditioned pain modulation (CPM) assesses descending pain pathways, crucial for understanding chronic pain.
  • Impaired CPM is common in chronic pain, highlighting its potential as a mechanistic indicator.
  • Lack of standardized protocols and reference data hinders clinical application of CPM.

Purpose of the Study:

  • To compare two CPM protocols with varying stimulus intensities and timing.
  • To evaluate CPM effect size, test-retest reliability, and sensitivity in detecting impaired pain inhibition.
  • To identify optimal CPM protocols for clinical use in individual patients.

Main Methods:

  • Compared two CPM protocols: one with 0°C water, another with 7°C water conditioning stimuli.
  • Assessed pressure pain threshold (PPT) and heat pain sensitivity.
  • Evaluated effect size (Cohen's d), test-retest reliability (ICC), and confidence intervals (CI).

Main Results:

  • 0°C water conditioning produced stronger PPT inhibition than 7°C water (d=0.52).
  • Testing during conditioning showed medium-to-large effects and good reliability for both PPT and heat pain.
  • 95% CIs for all outcomes included facilitation; the most sensitive measure for detecting abnormality was PPT after 0°C conditioning (decrease >75 kPa or 14% baseline).

Conclusions:

  • Testing CPM during conditioning stimulation offers good reliability and effect sizes.
  • Sequential CPM protocols, particularly PPT testing after 0°C water immersion, provide the narrowest CIs.
  • This approach facilitates CPM assessment beyond group averages, enabling individual comparisons in clinical settings.