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.