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.

The Psychosocial Characteristics and Somatosensory Function of Children and Adolescents Who Meet the Criteria for Chronic Nociplastic Pain

“…We used a recently established clinical criteria and grading system for chronic nociplastic pain affecting the musculoskeletal system to stratify our cohort as meeting or not meeting the criteria for nociplastic pain as a dominant pain mechanism. 2 , 5 , 11 We defined patients as meeting the criteria for nociplastic pain 5 when they have (1) regional pain rather than discrete/distinct in distribution, (2) with no evidence that nociceptive or neuropathic pain is entirely responsible for the pain, and (3) with the presence of evoked pain hypersensitivity that can be elicited clinically in the region of pain (ie presence of peripheral or central sensitization; allocated to a mechanical or thermal hyperalgesia somatosensory profile 12 ).…”

“…Available data were analyzed using R Studio and plotted using Prism-GraphPad. An average z-score (eg, z-score = affected site patient – control site patient cohort mean / control site patient cohort SD ) 12 for all QST parameters of the control and affected area was calculated for each patient. A positive z-score indicates a gain of function (hyperalgesia) while a negative score indicates a loss of function (sensory loss).…”

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

“…This has facilitated analysis of a large and novel cohort for investigation unlike our previously published work. 12 , 27 , 28 , 40 Between 2015 and 2021, patients were recruited in the spine or orthopedic outpatient clinics of the Shriners Hospitals for Children—Canada or by referral from the Chronic Pain Clinic from the Montreal Children's Hospital. Age-matched control subjects with no chronic pain were recruited between 2018 and 2021 through word of mouth, advertisements, and a collaborative high school nearby.…”

“…Conditioned pain modulation assessment was conducted using a protocol as previously described by our group. 12 , 27 , 28 , 40 Tests were conducted by research assistants, who were trained and evaluated by the principal investigator of the study, following rigorous standards of procedure to decrease between-tester variability. The thermode with a baseline of 32°C and a 0.3°C/s upslope was applied 3 times.…”

“…Our group has shown the heterogeneity of CPM efficiency and temporal summation in samples of patients with chronic musculoskeletal pain. 12 , 27 , 28 , 40 However, the pain modulation responses were considered separately and no association between facilitatory and inhibitory pain modulation responses were investigated or observed.…”