Phenotyping Chronic Musculoskeletal Pain in Male and Female Adolescents: Psychosocial Profiles, Somatosensory Profiles and Pain Modulatory Profiles

Abstract

Purpose: A major limitation in treatment outcomes for chronic pain is the heterogeneity of the population. Therefore, a personalized approach to the assessment and treatment of children and adolescents with chronic pain conditions is needed. The objective of the study was to subgroup pediatric patients with chronic MSK pain that will be phenotypically different from each other based on their psychosocial profile, somatosensory function, and pain modulation.

Patients and methods: This observational cohort study recruited 302 adolescents (10-18 years) with chronic musculoskeletal pain and 80 age-matched controls. After validated self-report questionnaires on psychosocial factors were completed, quantitative sensory tests (QST) and conditioned pain modulation (CPM) were performed.

Results: Three psychosocial subgroups were identified: adaptive pain (n=125), high pain dysfunctional (n=115), high somatic symptoms (n=62). Based on QST, four somatosensory profiles were observed: normal QST (n=155), thermal hyperalgesia (n=98), mechanical hyperalgesia (n=34) and sensory loss (n=15). Based on CPM and temporal summation of pain (TSP), four distinct groups were formed, dysfunctional central processing group (n=27) had suboptimal CPM and present TSP, dysfunctional inhibition group (n=136) had suboptimal CPM and absent TSP, facilitation group (n=18) had optimal CPM and present TSP, and functional central processing (n=112) had optimal CPM and absent TSP. A significant association between the psychosocial and somatosensory profiles. However, no association was observed between the psychosocial or somatosensory profiles and pain modulatory profiles.

Conclusion: Our results provide evidence that adolescents with chronic musculoskeletal pain are a heterogenous population comprising subgroups that may reflect distinct mechanisms and may benefit from different treatment approaches. The combination of screening self-reported questionnaires, QST, and CPM facilitate subgrouping of adolescents with chronic MSK pain in the clinical context and may ultimately contribute to personalized therapy.

Keywords: adolescents; chronic pain; conditioned pain modulation; musculoskeletal pain; quantitative sensory testing; temporal summation of pain.

Figure 1

Flow chart of patient recruitment and evaluations.

Figure 2

Inhibitory and facilitatory pain modulations responses in adolescents with chronic musculoskeletal pain and age-matched controls. The distribution of conditioned pain modulation in (A) patients and (a) age-matched controls show a spectrum of individual responses. Bar = individual participants. A CPM efficiency between −100% and −30% was considered as optimal, between −30% and −10% suboptimal and between −10% and +100% inefficient. The distribution of temporal summation of pain during the test stimulus before the conditioning stimulus in (B) patients and (b) age-matched controls also show a spectrum of individual responses. Bar = individual participants. An increase in pain intensity was determined minimum clinically significant if the change was equal or larger than 20/100 during the last 60 seconds of the first test stimulus (ie, presence of temporal summation of pain).

Figure 3

Psychosocial profiles in adolescents with chronic musculoskeletal pain. (A) Individual patient questionnaire scores were transformed and presented as z-scores. Higher z-scores represent higher scores for the questionnaire completed. Differences are significant if p<0.05 Significant difference between ^#the adaptive pain and high pain dysfunctional cluster, ^‡the adaptive pain and high somatic symptoms cluster or ^†the high pain dysfunctional and high somatic symptoms cluster. Data points = mean. (B) The pain catastrophizing score is represented by psychosocial cluster and compared with age-matched controls. Bars = mean ± SEM. (C) The Revised Child Anxiety and Depression Scale total T-score is represented by psychosocial cluster and compared with age-matched controls. Bars = mean ± SEM. (D) The Pittsburgh Sleep Quality Index global score is represented by psychosocial cluster and compared with age-matched controls. Bars = mean ± SEM. *p<0.05, **p<0.01, ****p<0.0001. PCS-C, pain Catastrophizing Scale – Child version; DN4, Douleur Neuropathique 4 questionnaire; FDI, Functional disability inventory; Sensory, sensory descriptors; Affective, affective descriptors; Evaluative, evaluative descriptors; Temporal, temporal descriptors; RCADS, Revised Child Anxiety and Depression Scale.

Figure 4

Quantitative sensory testing profiles in adolescents with chronic musculoskeletal pain. Individual patient pain area thresholds were converted into z-scores calculated with reference to within-cohort control measures at the control area. Individual patient control area thresholds were converted into z-scores calculated with reference to between-cohort control measures at the control area. z-Scores for dynamic mechanical allodynia to brush and for the presence of painful after-sensations at the end of the 60-second period after 10 pinprick stimuli were were calculated with reference to the pain intensity reported by the patients using the numerical rating scale (NRS 0–10). An average z-score for all QST parameters for the control and affected area was then calculated for each patient. The z-score plot for each individual patient was grouped according to the closest matching adult mechanism-related profile: mechanical hyperalgesia, sensory loss, thermal hyperalgesia or normative QST. Gain of function (hyperalgesia) is indicated as a positive z-score and a loss of function (sensory loss) as a negative score. Data points = mean.

Figure 5

Pain modulation profiles in adolescents with chronic musculoskeletal pain and age-matched controls. Mean pain intensity during the tonic thermal heat stimulations of the conditioned pain modulation assessment. Each individual patient was grouped according to their inhibitory and facilitatory pain modulation responses: dysfunctional central processing (suboptimal or inefficient CPM and presence of temporal summation of pain), dysfunctional inhibition (suboptimal or inefficient CPM and absence of temporal summation of pain), facilitation (optimal CPM and presence of temporal summation of pain) and functional central processing (optimal CPM and absence of temporal summation of pain). A CPM efficiency between −100% and −30% was considered as optimal, between −30% and −10% suboptimal and between −10% and +100% inefficient. Presence of temporal summation of pain was defined as an increase in pain intensity equal or larger than 20/100 (using the CoVAS) during the last 60 seconds of the first test stimulus.

Figure 6

Associations between psychosocial profiles and somatosensory profiles and pain modulatory profiles. (A) The proportion of distinct somatosensory profiles is shown divided by the identified psychosocial profiles. (B) The proportion of distinct pain modulatory profiles is shown divided by the identified psychosocial profiles. (C) The proportion of distinct somatosensory profiles is shown divided by the identified pain modulatory profiles.

Figure 7

Comprehensive patient pain assessment and rational predicted treatment efficacy. Pain assessment through self-reported questionnaires, quantitative sensory testing and conditioned pain modulation identifies distinct psychosocial, somatosensory, and pain modulatory profiles. Predictions for differential efficacy of treatment approaches across profiles are depicted. + represents beneficial; ++ represents very beneficial.