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

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.

Individual variability and sex differences in conditioned pain modulation and the impact of resilience, and conditioning stimulus pain unpleasantness and salience.

Distinct pain experiences are shaped both by personal attributes and characteristics of noxious stimuli. An Individual's capacity for endogenous pain inhibition (reflected by conditioned pain modulation [CPM]), their resilience, and the pain unpleasantness and salience of painful stimuli can impact their pain perception. Here, we aimed to determine how individual variability in CPM relates to sex and resilience as personal attributes, and pain unpleasantness and salience of the CPM conditioning stimulus (CS). We evaluated CPM in 106 healthy participants (51 female and 55 male) based on the change in test stimulus pain applied concurrently with a painful CS, both delivered by painful heat. The CS reduced test stimulus pain in only half of the participants (CPM subgroup), but did not do so for the other half (no-CPM subgroup), many who exhibited pain facilitation. A regression model explained CPM effects after accounting for sex, resilience, CS pain unpleasantness and salience. In the CPM subgroup regression model, the CPM effect was positively related to CS pain unpleasantness, while the CPM effect was not related to any variable in the no-CPM subgroup model. Correlation analyses revealed that the CPM effect was anticorrelated with resilience in males with no-CPM. The CPM effect was correlated with CS pain unpleasantness in males with CPM and in females with no-CPM. The CPM effect and CS salience were correlated in the whole group more strongly than in the subgroups. These data reveal that the complexity of contributors to CPM variability include both personal attributes and attributes of the CS.

Chronic pain: breaking free from stickiness.

By introducing the concept of "pain stickiness" underlying treatment-resistant pain, Borsook et al. take a neurobiological perspective to capture the factors that may contribute to the transition of pain from acute to chronic form. However, there is more to consider, including the interconnected influences of resilience, brain gray matter and connectivity, sex differences, and the role of the environment. There still remains the question of how to eliminate this stickiness.