Neurobiology of Pain in Burn Survivors

Pain is particularly prevalent (>50%) and disabling following burn injuries. Chronic pain is strongly modulated by negative affect, and pain catastrophizing, a pain-specific psychosocial construct comprising helplessness, pessimism, rumination, and magnification about pain-related symptoms, is a critical predictor of pain severity and treatment satisfaction. Non-pharmacologic interventions such as Cognitive Behavioral Therapy (CBT) improve pain partially by reducing catastrophizing. However, the underlying neurobiology supporting catastrophizing in burn injury survivors remains understudied. Identifying objective, catastrophizing-linked neural biomarkers may serve as important therapeutic targets and predict clinical treatment response.

This study is a randomized, longitudinal neuroimaging trial evaluating the mechanisms of CBT compared to an active educational control. Participants with chronic burn pain are randomized in a 1:1 ratio to undergo one of two 8-week, remotely delivered interventions:

• CBT: Features 8 weekly 60-minute virtual sessions using active, structured cognitive-behavioral techniques. The intervention focuses on acquiring and practicing cognitive and emotional modulatory skills (e.g., relaxation, thought-stopping, distraction, cognitive restructuring) to reduce maladaptive pain-related cognitions.
• Pain Education (EDU): An active control condition matched for professional contact time, consisting of 8 weekly virtual sessions covering general pain-related topics (e.g., Gate-Control Theory, pain types) without active pain-coping skill acquisition or home practice.

Assessments and Imaging:

Assessments take place at baseline, 8 weeks (post-intervention), and 24 weeks (follow-up).

• Neuroimaging: Participants undergo 3-Tesla brain MRI sessions at baseline and 8 weeks, including structural MRI, resting-state fMRI, and a pain catastrophizing fMRI task.
• fMRI Task: Patients view and reflect on statements from the Pain Catastrophizing Scale (PCS) intermixed with matched neutral statements in a block design during functional scanning.
• Sensory and Clinical Measures: Baseline visits include Quantitative Sensory Testing (QST) via cuff pressure algometry.
• Validated questionnaires are administered at all timepoints to measure pain interference (Brief Pain Inventory), catastrophizing (PCS), coping, self-efficacy, and general psychosocial functioning (PROMIS-29).

Study Aims

• Aim 1: Investigate the association between brain processing of catastrophizing and individual differences in pain intensity and interference among burn-injury survivors. H1.1: Patients with more burn-associated pain and worse interference will show greater catastrophizing-induced activation in posterior cingulate cortex (PCC). H1.2: Patients with more pain and interference will also show greater catastrophizing-induced connectivity between PCC and salience network regions, such as anterior mid-cingulate cortex (aMCC).
• Aim 2: Evaluate whether CBT (compared to pain education (EDU)) results in greater improvement in pain and catastrophizing, and reduced brain response to catastrophizing cues. H2.1: Patients randomized to CBT, compared to EDU, will report greater reductions in pain interference and catastrophizing. H2.2: Patients randomized to CBT, compared to EDU, will show greater reduction in PCC responses to catastrophizing cues. H2.3: Greater reduction in catastrophizing will be correlated with greater reduction in PCC responses.
• Aim 3: Determine whether baseline PCC response to catastrophizing cues (after controlling for patient-reported catastrophizing scores) predicts improvement in pain outcomes following CBT, and whether changes in PCC catastrophizing response mediate changes in pain outcomes. H3.1: Based on our preliminary data, greater aMCC activation and PCC-to-aMCC connectivity response to catastrophizing cues at baseline will predict greater reductions in pain interference and catastrophizing following CBT (but not EDU). H3.2: Change in catastrophizing cue PCC responses following therapy will mediate the improvements in pain interference following CBT (versus EDU).

Inclusion criteria

• Previously hospitalized for burn injury
• Age 18 to 65 years
• Able to provide written informed consent and fluent in English
• Living in a community setting
• Six (6) months or more post-burn injury
• Burn-related pain rated as ≥4 (on a scale of 0-10) over the past week, co-localized with the site of the burn injury

Exclusion criteria

• Comorbid acute pain condition.
• Comorbid chronic pain condition that is rated by the participant as more painful than the burn injury pain.
• Living in an institution or medical facility.
• Pregnant or nursing.
• Any psychiatric condition precluding study participation, such as a disorder involving psychosis (e.g., schizophrenia), unmanaged bipolar disorder, or a severe personality disorder.
• History of anxiety disorders or significant anxiety symptoms interfering with imaging procedures (e.g., panic).
• Contraindication to MRI (e.g., implanted ferrous metal).
• History of significant head injury (e.g., with substantial loss of consciousness).
• Psychiatric hospitalization in the past 6 months.
• Currently participating in therapeutic clinical research trials.