Phenotyping peripheral neuropathic pain in male and female adolescents

Neuropathic pain (NeuP) can be difficult to diagnose and manage in children. Data regarding prevalence and sex-dependent differences are limited, and more detailed phenotyping is needed. This observational cohort study recruited adolescents (10-17 years) with NeuP or complex regional pain syndrome (CRPS). After pain history and NeuP questionnaires, quantitative sensory testing was performed. Individual z-score plots were calculated with body-region control measures and matched to mechanism-related sensory profiles (sensory loss, thermal hyperalgesia, and mechanical hyperalgesia). Conditioned pain modulation was assessed with pressure pain threshold and a contralateral cold conditioning stimulus, and meaningful conditioned pain modulation defined as twice the standard error of measurement. Patients and parents completed validated questionnaires for child quality of life (QoL), pain catastrophizing, and self-reported anxiety/depression. Males (n = 23) and females (n = 43) with NeuP (n = 52) or CRPS (n = 14) reported moderate–severe pain with neuropathic sensory descriptors. Mixed patterns of sensory gain/loss at pain sites were not sex-dependent. Thermal hyperalgesia was common in both NeuP and CRPS, whereas sensory loss occurred only with NeuP and in a smaller proportion than adult cohorts. Conditioned pain modulation was inhibitory in 54%, facilitatory in 14%, and nonresponders had variable cold conditioning sensitivity. Males and females reported marked impairment of QoL, increased emotional distress, and pain catastrophising. Child–parent QoL scores correlated, but catastrophizing scores were discordant when parents or adolescents reported higher anxiety/depression. NeuP in adolescents is associated with significant pain, physical impairment, and psychosocial impairment. Quantifying alterations in somatosensory profiles, descending modulation, child and parent psychological function will inform individualized therapy and stratification for future clinical trials