Chronic Pain After Combat-Related Traumatic Brain Injury (cTBI-Pain Study) A Prospective Cohort Study of Pain Chronification After Combat-Related Traumatic Brain Injury

Overview

Combat-related traumatic brain injury (cTBI), particularly blast-related injury, is frequently associated with the development of persistent and disabling chronic pain. This prospective observational cohort study aims to determine the incidence, phenotypes, and early predictors of chronic pain following mild to moderate combat-related TBI. Adults will be enrolled within 14 days of injury and followed for 6 months. The primary endpoint is clinically significant chronic pain at 3 months, defined by pain intensity and functional interference. The study will evaluate clinical, psychological, and physiological factors to develop and internally validate a prognostic model for chronic pain risk after cTBI.

Combat-related traumatic brain injury (cTBI), particularly blast-associated injury, is a major contributor to the development of chronic pain syndromes in military populations. Pain following cTBI may present as chronic post-traumatic headache, cervicogenic pain, neuropathic pain, or widespread pain associated with central sensitization. The interaction between neuronal injury, psychological stress (including PTSD), sleep disturbance, and associated peripheral trauma creates a high-risk environment for pain chronification. This prospective observational cohort study will enroll adults with mild to moderate combat-related traumatic brain injury within 14 days of injury. Participants will undergo standardized clinical, psychometric, and physiological assessments during the acute phase and will be followed longitudinally at 6 weeks, 3 months, and 6 months. Pain intensity will be assessed using the Numerical Rating Scale (NRS) and the Brief Pain Inventory (BPI). Neuropathic pain features will be evaluated using DN4, and central sensitization symptoms using the Central Sensitization Inventory (CSI). Psychological factors including PTSD (PCL-5), depression (PHQ-9), anxiety (GAD-7), and pain catastrophizing (PCS) will be assessed. Sleep disturbance will be evaluated using the Insomnia Severity Index (ISI). Functional outcomes will be measured using WHODAS 2.0 and PROMIS Physical Function. A subgroup of participants will undergo physiological testing, including heart rate variability (HRV) and quantitative sensory testing (QST). The primary endpoint is clinically significant chronic pain at 3 months, defined as NRS ≥4 and/or BPI interference score ≥4. Secondary outcomes include neuropathic pain phenotype, functional impairment, psychological outcomes, and persistent analgesic use at 6 months. Multivariable regression modeling, including logistic regression and penalized methods (LASSO), will be used to identify independent predictors of chronic pain. Internal validation will be performed using bootstrapping techniques. Model performance will be evaluated using ROC-AUC and calibration metrics. The study aims to develop a clinically applicable risk prediction model to identify individuals at high risk for chronic pain following combat-related TBI and to inform early preventive and rehabilitative interventions.