Deriving groups of individuals with differing treatment response trajectories stimulates new thinking regarding potential mechanisms that may be driving these outcomes.
Objective
The purpose of this study was to explore brain morphological and functional connectivity alterations in adolescents with new daily persistent headache (NDPH) compared to pain‐free, healthy controls.
Background
NDPH is one of the most disabling and least understood primary headache conditions. To date, no studies have considered the role of brain function and structure in pediatric patients with NDPH.
Methods
In this cross‐sectional study, resting‐state functional and structural images were acquired for 13 patients with NDPH (M age = 15.9, standard deviation [SD] ± 1.4) and 13 age‐ and sex‐matched controls (M age = 16.2, SD ± 1.8) using magnetic resonance imaging. Participants were recruited from the Pediatric Headache Program at Boston Children's Hospital and from the Greater Boston area. In patients, clinical features of NDPH, including disease duration, pain intensity ratings, pain sensitivity, and functional disability were also assessed, and their associations with functional and structural brain alterations were explored.
Results
Compared to controls, patients with NDPH demonstrated reduced cortical thickness in the bilateral superior temporal gyrus, left superior, and middle frontal gyrus areas (p < 0.05, Monte Carlo corrected for multiple comparisons). Furthermore, reduced cortical thickness of the left superior frontal gyrus was related to elevated pain sensitivity in NDPH (r = −0.79, p = 0.006). Patients showed altered functional connectivity between regions involved in emotional and cognitive networks of pain, including the amygdala, insula, frontal regions, and cerebellar subregions.
Conclusion
The present study provides the first preliminary evidence of functional and structural brain differences in pediatric patients with NDPH compared to controls. Identifying alterations in cortical thickness and resting‐state connectivity between specific brain regions could provide characteristics of NDPH and probable mechanisms that may guide personalized therapeutic interventions.
Offset analgesia (OA), a psychophysical test of endogenous pain inhibition, is diminished in many adult chronic pain disorders but OA has not been investigated in youth with chronic pain disorders. This study assessed OA responses in 30 youth with chronic primary and secondary pain disorders and 32 healthy controls. The OA, control, and constant thermal tests were evoked with an individualized noxious heat stimulus of approximately 50/100 mm on a visual analogue scale followed by 1°C offset temperature. This study also examined the association of OA responses with 2 self-report measures of pain sensitivity, the Central Sensitization Inventory (CSI) and Pain Sensitivity Questionnaire. Patients exhibited diminished capacity to activate OA with a reduction in ΔeVASc of 53 ± 29% vs controls 74 ± 24% (P = 0.003) even after multivariate regression adjusting for age, sex, and body mass index. Patients also showed decreased ability to habituate to a constant noxious heat stimulus compared to controls (P = 0.021). Central Sensitization Inventory scores showed excellent predictive accuracy in differentiating patients from controls (area under the curve = 0.95; 95% CI: 0.91-0.99) and CSI score ≥30 was identified as an optimal cutoff value. Pain Sensitivity Questionnaire scores did not differentiate patients from controls nor correlate with OA. In this study, 60% of youth with chronic pain showed reduced capacity for endogenous pain inhibition.
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