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. 2022 Oct 4;7(6):e1032.
doi: 10.1097/PR9.0000000000001032. eCollection 2022 Nov-Dec.

Clusters of facilitatory and inhibitory conditioned pain modulation responses in a large sample of children, adolescents, and young adults with chronic pain

Don Daniel Ocay  1   2   3 , Diana-Luk Ye  1   2 , Cynthia L Larche  2 , Stéphane Potvin  4 , Serge Marchand  5 , Catherine E Ferland  1   2   3   6
Affiliations

Clusters of facilitatory and inhibitory conditioned pain modulation responses in a large sample of children, adolescents, and young adults with chronic pain

Don Daniel Ocay et al. Pain Rep. .

Abstract

Introduction: When investigating the role of facilitatory and inhibitory pain mechanisms such as conditioned pain modulation (CPM) and temporal summation of pain (TSP), it is important to take both into consideration in a single experimental model to provide the most information on subgroups of patients. Therefore, the objective of this study was to identify subgroups in a large population of pediatric patients with chronic pain based on their facilitatory and inhibitory pain mechanisms and compare them with control subjects.

Methods: Five hundred twenty-one female subjects and 147 male subjects between 8 and 21 years old underwent a CPM assessment using a 2-minute tonic noxious heat stimulation as the test stimulus and a 2-minute cold-pressor task (CPT) (12°C) as the conditioning stimulus.

Results: The best partition of clusters of patients was 3 clusters accounting for 27.15% of the total variation in the data. Cluster 1 (n = 271) was best characterized by high pain intensity during the CPT, lack of TSP during the test stimuli, and efficient inhibitory CPM. Cluster 2 (n = 186) was best characterized by low pain intensity during the CPT, lack of TSP during the test stimuli, and efficient inhibitory CPM. Cluster 3 (n = 151) was best characterized by high pain intensity during the CPT, presence of TSP during the test stimuli, and inefficient inhibitory CPM.

Discussion: A single thermal CPM experimental design can identify combinations of facilitatory and inhibitory pain modulation responses. Findings from the current study add to the literature by describing different clinical phenotypes of central pain mechanisms of youth with chronic pain.

Keywords: Chronic pain; Cluster; Conditioned pain modulation; Control; Pediatric.

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Conflict of interest statement

The authors have no conflicts of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Figures

Figure 1.
Figure 1.
(A) Distribution of conditioned pain modulation (CPM) efficiency of the patient sample in which each bar represents one patient (n = 608). A negative value represents pain inhibition, whereas a positive value represents pain facilitation. The gray dotted lines mark the cutoffs for optimal (n = 293), suboptimal (n = 129), and inefficient (n = 186) CPM efficiency. (B–D) Mean pain intensity during the tonic thermal heat stimulations of the patients based on the different patterns of the CPM score: (B) optimal, (C) suboptimal, and (D) inefficient. A greater percentage difference in pain intensity during the tonic thermal heat stimulations demonstrates a greater CPM efficiency. CoVAS, computerized visual analog scale.
Figure 2.
Figure 2.
(A) Distribution of the change in pain intensity during the tonic thermal heat stimulation before the conditioning stimulus (TS1) of the patient sample in which each bar represents one patient (n = 608). The gray dotted line marks the cutoffs for a significant decrease of −20/100 (n = 91), no change (n = 430), and a significant increase of 20/100 (n = 87) in pain intensity. (B–D) Mean pain intensity during the last 60 seconds of the tonic thermal heat stimulation before the conditioning stimulus of the patients based on the different patterns of change in pain intensity: (B) a decrease, (C) no change, or (D) an increase in pain intensity. CoVAS, computerized visual analog scale.
Figure 3.
Figure 3.
(A) Distribution of the change in pain intensity during the tonic thermal heat stimulation after the conditioning stimulus (TS2) of the patient sample, in which each bar represents one patient (n = 608). The gray dotted line marks the cutoffs for a significant decrease of −20/100 (n = 57), no change (n = 465), and a significant increase of 20/100 (n = 86) in pain intensity. (B–D) Mean pain intensity during the last 60 seconds of the tonic thermal heat stimulation after the conditioning stimulus of the patients based on the different patterns of change in pain intensity: (B) a decrease, (C) no change, or (D) an increase in pain intensity. CoVAS, computerized visual analog scale.
Figure 4.
Figure 4.
(A) Bar and (B) scatter plot of the indicator variables respective of the 3 clusters derived from the hierarchical cluster analysis with k-means. A score of zero is aligned with the mean of the sample. The P values of Fisher pairwise comparisons are shown. *P < 0.05; **P < 0.01; ***P < 0.05; ****P < 0.01. Bars = mean ± SEM. Points = individual patients. TSP1, change in pain intensity during last 60 seconds of the first test stimulus; CS, conditioning stimulus; TSP2, change in pain intensity during last 60 seconds of the second test stimulus; CPM; conditioned pain modulation efficiency. Patients grouped in cluster 1 are characterized by significantly lower values for TSP1, TSP2, and CPM efficiency compared with cluster 2 and 3. Patients grouped in cluster 3 are characterized by significantly higher values for TSP1, TSP2, and CPM efficiency compared with cluster 1 and 2. Patients in cluster 2 are characterized to have significantly lower values for CS compared with cluster 1 and 3.
Figure 5.
Figure 5.
Mean pain intensity during the tonic thermal heat stimulations (A–D) and cold-pressor task (a–d) for each patient cluster and healthy control subjects. CoVAS, computerized visual analog scale; NRS, numerical rating scale.
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