The Potential Clinical Utility of Pressure-Based vs. Heat-Based Paradigms to Measure Conditioned Pain Modulation in Healthy Individuals and Those With Chronic Pain.

Rima El-Sayed,Natalie R Osborne,Camille Fauchon,Junseok A Kim,Ariana Besik,Shahrzad Firouzian,Emily P Mills,Karen D Davis,Anuj Bhatia

doi:10.3389/fpain.2021.784362

Abstract

Conditioned pain modulation (CPM) is a physiological measure thought to reflect an individual's endogenous pain modulation system. CPM varies across individuals and provides insight into chronic pain pathophysiology. There is growing evidence that CPM may help predict individual pain treatment outcome. However, paradigm variabilities and practical issues have impeded widespread clinical adoption of CPM assessment. This study aimed to compare two CPM paradigms in people with chronic pain and healthy individuals. A total of 30 individuals (12 chronic pain, 18 healthy) underwent two CPM paradigms. The heat CPM paradigm acquired pain intensity ratings evoked by a test stimulus (TS) applied before and during the conditioning stimulus (CS). The pressure CPM paradigm acquired continuous pain intensity ratings of a gradually increasing TS, before and during CS. Pain intensity was rated from 0 (no pain) to 100 (worst pain imaginable); Pain50 is the stimulus level for a response rated 50. Heat and pressure CPM were calculated as a change in TS pain intensity ratings at Pain50, where negative CPM scores indicate pain inhibition. We also determined CPM in the pressure paradigm as change in pressure pain detection threshold (PDT). We found that in healthy individuals the CPM effect was significantly more inhibitory using the pressure paradigm than the heat paradigm. The pressure CPM effect was also significantly more inhibitory when based on changes at Pain50 than at PDT. However, in individuals with chronic pain there was no significant difference in pressure CPM compared to heat or PDT CPM. There was no significant correlation between clinical pain measures (painDETECT and Brief Pain Inventory) and paradigm type (heat vs. pressure), although heat-based CPM and painDETECT scores showed a trend. Importantly, the pressure paradigm could be administered in less time than the heat paradigm. Thus, our study indicates that in healthy individuals, interpretation of CPM findings should consider potential modality-dependent effects. However, in individuals with chronic pain, either heat or pressure paradigms can similarly be used to assess CPM. Given the practical advantages of the pressure paradigm (e.g., short test time, ease of use), we propose this approach to be well-suited for clinical adoption.

Highlights

Conditioned pain modulation (CPM) is a behavioral phenomenon that reflects an individual’s inherent capacity to modulate their pain
Our main findings were that 1) in healthy individuals, the pressure-based paradigm produced a stronger inhibitory CPM compared to the heat-based paradigm, and most participants exhibited modality-dependent CPM effects, 2) in people with chronic pain, there was no significant difference in the CPM evoked by the pressure- and heat-based paradigms, with the majority exhibiting modalityindependent CPM effects, 3) the pressure paradigm evoked a similar or more inhibitory CPM effect when calculating CPM based on the Pain50 level compared to the pain detection threshold (PDT), 4) The healthy group had a significantly more inhibitory CPM than the chronic pain group in the pressure paradigm but not the heat paradigm
Our findings indicate that the interpretation of CPM effects in healthy individuals needs to consider the stimulus modality and metric used to calculate CPM

Summary

Introduction

Conditioned pain modulation (CPM) is a behavioral phenomenon that reflects an individual’s inherent capacity to modulate their pain. The CPM effect [a term coined by Yarnitsky et al [5]] refers to any change in the intensity of pain that is evoked by a test stimulus (TS) applied to one area of the body due to the presence of a concurrent conditioning stimulus (CS) applied to another area of the body [6]. This psychophysical measure of CPM designed for testing in humans was motivated by the discovery of the diffuse noxious inhibitory control (DNIC) effect observed in animal electrophysiological single neuronal recordings. It is clear that CPM can vary across a wide spectrum, from reduced pain due to the presence of a CS (inhibitory CPM) to increased pain (facilitatory CPM), and in some cases CPM may not occur at all (no-CPM) [6, 11, 12]

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