Neurobiology of Pain in Burn Survivors

N/ANot Yet RecruitingNCT07824635

Spaulding Rehabilitation Hospital92 enrolled

Overview

Many burn survivors experience persistent, disabling pain that is strongly influenced by pain catastrophizing, a pattern of negative cognitive and emotional responses to pain involving feelings of helplessness, rumination, and magnification of symptoms. The primary purpose of this study is to evaluate whether an 6-week, remotely delivered cognitive-behavioral therapy program reduces pain interference (disruption to daily life) and pain catastrophizing more effectively than an 6-week pain education. Researchers also aim to identify the neurobiological mechanisms through which non-pharmacologic pain management works using functional Magnetic Resonance Imaging brain scans.

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 6-week, remotely delivered interventions: * CBT: Features 6 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 6 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, 6 weeks (post-intervention), and 24 weeks (follow-up). * Neuroimaging: Participants undergo 3-Tesla brain MRI sessions at baseline and 6 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).

Interventions

Cognitive Behavioral TherapyBEHAVIORAL

An 6-week, remotely delivered behavioral intervention administered weekly via secure video conferencing by a trained psychologist (approximately 60 minutes per session). It utilizes active, structured techniques (such as relaxation, thought-stopping, distraction, and cognitive restructuring) along with in-vivo and home practice to target and reduce maladaptive pain-related cognitions (i.e., pain catastrophizing).

Pain EducationBEHAVIORAL

An 6-week, remotely delivered educational control intervention administered weekly via secure video conferencing by a trained psychologist (approximately 60 minutes per session). Matched for therapist contact time with the Cognitive Behavioral Therapy group, sessions cover standard pain-related topics (e.g., Gate-Control Theory, types of chronic pain, working with healthcare providers) without active skill-building components, handouts, or at-home practice.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

fMRI Measure

Participants will undergo functional MRI scan sessions, including resting-state fMRI and task-based BOLD fMRI. Task-based fMRI utilizes a block-design contrasting 6 Pain Catastrophizing Scale statements (covering helplessness, magnification, and rumination) against 6 lexically matched neutral control statements.

Time frame: Baseline and 6 weeks (post-intervention).

Secondary Outcomes

Pain Catastrophizing Scale (PCS)

The Pain Catastrophizing Scale (PCS) will be used to evaluate negative cognitive-emotional responses to pain across three subscales: helplessness, magnification, and rumination. Scores range from 0 to 52, with higher scores indicating greater pain catastrophizing (worse outcome).

Time frame: Baseline, 6 weeks (post-intervention), and 24 weeks (follow-up).

Brief Pain Inventory (BPI)

Measured using the Brief Pain Inventory (BPI) Pain Interference subscale. Evaluates how pain impacts daily activities, mood, mobility, work, relationships, sleep, and enjoyment of life on a scale of 0 to 10, where higher scores indicate greater pain interference (worse outcome).

Time frame: Baseline, 6 weeks (post-intervention), and 24 weeks (follow-up)