Development of a new bed-side-test assessing conditioned pain modulation: a test-retest reliability study
Authors: Larsen Jesper Bie , Madeleine Pascal , Arendt-Nielsen Lars 
Published: March 2019

Abstract

Background and aims
Conditioned pain modulation (CPM) is of considerable interest within pain research. Often CPM testing is conducted in experimental settings using complicated instrumentation, thus challenging the implementation in clinical settings. Being able to assess CPM in a fast and reliable way in clinical settings could lead to a new diagnostic tool allowing improved profiling of pain patients.

Methods
A test-retest reliability study and a methodological development study were conducted based on different populations. The reliability study included 22 healthy subjects, mean age 23.6 years (SD: 2.4) and the methodological study included 29 healthy subjects, mean age 21.5 years (SD: 1.6). As painful phasic test stimulus, a 6–10 kg handheld, spring-based pressure algometer was applied perpendicularly to the muscle belly of the tibialis anterior muscle for 10 s and as painful tonic conditioning stimulus, 1–2 standard clamps, inducing a force of 1.3 kg, were applied extra-segmentally at the ipsilateral earlobe for 60–120 s. Four different test protocols were evaluated, of which one protocol was investigated for reliability. Test protocol 1 used a 6 kg pressure algometer as painful phasic test stimulus and a single clamp applied for 60 s as painful tonic conditioning stimulus. Test protocol 2 used a 10 kg pressure algometer as painful phasic test stimulus, and two clamps applied for 60 s as painful tonic conditioning stimulus. Test protocol 3 used a 10 kg pressure algometer as painful phasic test stimulus and a single clamp applied for 120 s as painful tonic conditioning stimulus. Test protocol 4 used a 6 kg pressure algometer as painful phasic test stimulus and a single clamp applied for 120 s as painful tonic conditioning stimulus.

Results
None of the stimuli caused any adverse events, e.g. bruises. In the reliability study (test protocol (1), non-significant CPM effects of 0.3 (SD: 1.6) and 0.2 (SD: 1.0) were observed in session 1 and 2, respectively. The intra-class correlations were 0.67 and 0.72 (p = < 0.01) and limits of agreement (LoA) ranged from −2.76 to 3.31. Non-significant CPM effects of 0.2 (SD: 1.0), −0.1 (SD: 1.1), and 0.0 (SD: 1.2) were observed for test protocol 2, 3, and 4, respectively).

Conclusions
The bedside test developed for investigating CPM was feasible and easy to use in healthy volunteers. No significant CPM effects were measured and a large variation in CPM effect ranging from −0.14 to 0.32 was observed. Intra-class correlation (ICC) values for the pressure algometer were interpreted as “good relative reliability” (test protocol 1), and LoA revealed a somewhat low absolute reliability.

Implications
The pressure algometer provided reproducible measurements and was useful for inducing phasic test stimuli. Since no significant CPM effects were detected, no recommendations for the bedside test can yet be made. Further examinations will have to establish if the “one size fits all” application of both test and conditioning stimuli is useful. Future bedside studies involving patient populations are warranted to determine the usefulness of the method.