Neural Mechanisms of Whole-Health Lifestyle Strategies for Lupus

Despite major advances in immunosuppressive treatment, many people living with systemic lupus erythematosus (SLE) continue to experience pain which interferes with daily activities and reduces overall well-being. Pain in SLE is particularly challenging because it is not only due to underlying autoimmune related inflammation but also influenced by many non-inflammatory factors.  Stress, mood, sleep disturbance, and social factors also shape how pain is experienced. Because of this, individuals with pain benefit from lifestyle-based approaches including stress reduction, mindfulness, gentle movement, healthy diet and education about how pain works in the brain. Although, these approaches can improve the impact and severity of pain, the biologic reasons why they help are not well understood.

The Whole Health Empowerment for Lupus (WHEEL) program is a 12-week online lifestyle program led by certified health coaches designed to help people with SLE better manage symptoms and improve quality of life.  In this mechanistic clinical trial, we aim to understand how the WHEEL program may influence the brain and reduce pain in up to 20 adults with SLE who report on-going pain despite standard medical therapy.  We hypothesize that WHEEL improves pain by influencing how central nervous system process pain signals. Specifically, we are focusing on two key brain systems that strongly influence how pain is interpreted:  the brain’s threat processing system, which responds to stress and danger, and the brain’s reward and motivation system which supports positive-reinforcement, pleasure, and goal-directed coping behavior. These two systems are modifiable and are directly engaged by core aspects of the WHEEL program including stress management, mindfulness, social support and self-management skills.

Participants in the study will complete the WHEEL program including the on-line small-group sessions, individual health coach sessions, educational notebook, and video tutorials to learn tools for emotional and physical wellbeing.  Before and after the 12-week intervention, participants will undergo functional magnetic resonance imaging (fMRI) scans of the brain, complete questionnaires about pain, emotions, and quality of life and have assessment of lupus disease activity.  These assessments will allow us to determine the psychological and neurological mechanisms of improvement.

The study aims to evaluate whether the WHEEL programs helps reduce overactivity in threat-related regions of the brain and improves activity in reward/motivation-related areas of the brain. By integrating brain imaging, clinical data, and patient experiences, this research seeks to uncover the biological and psychological mechanisms behind chronic pain in SLE. Ultimately, the findings of this study could provide valuable insights into new therapeutic approaches for improving quality of life in individuals living with this complex disease.

Despite significant advances in targeted immunosuppressant therapy, many individuals living with systemic lupus erythematosus (SLE) experience persistent pain which interferes with daily functioning and diminishes quality of life.  Pain in SLE is particularly complex, arising from interconnected neural pathways influenced not only by disease-related inflammation but also non-inflammatory psychosocial and environmental factors.  Stress, mood disorders, sleep disruption, prior trauma, and social isolation can shape how pain is perceived and processed. Given this multifactorial etiology, individuals with pain benefit from lifestyle-based management strategies including stress reduction, mindfulness, restorative movement, balanced diet and neuroscience pain education. Although these approaches can improve the impact and severity of pain, the neural mechanisms underlying their benefit remain poorly understood.

The Whole Health Empowerment for Lupus (WHEEL) program is a 12-week multimodal virtual lifestyle program led by certified health coaches designed to help people with SLE better manage symptoms and improve quality of life.  The overarching goal of this mechanistic clinical trial is to understand how the WHEEL program may influence the neural pathways involved in pain processing in up to 20 adults with SLE who report on-going pain despite standard-of- care therapy.  We hypothesize that WHEEL improves pain by influencing how the central nervous system process pain signals. Specifically, we are focusing on two key brain circuits that strongly influence pain interpretation:  the threat processing circuit, which responds to stress and danger, and the reward and motivation circuit which supports positive-reinforcement, pleasure, and goal-directed coping behavior. These circuits are modifiable and are directly engaged by core aspects of the WHEEL program including stress management, mindfulness, social support and self-management skills. Participants in the study will complete the WHEEL program which includes nine on-line small-group sessions, three individual health coach sessions, an educational notebook curriculum, and video tutorials that provide skills for emotional  and physical well-being.

The study has two primary objectives. First, we aim to elucidate psychological mechanisms through which WHEEL improves central processing of pain in SLE. This will be evaluated using self-reported and physically evoked pain outcomes via quantitative sensory testing, and patient-reported measures capturing threat and reward domains. Second, we aim to determine the neural mechanisms by which WHEEL modifies central pain processing through pre- and post- intervention resting-state functional magnetic resonance imaging (fMRI) of the brain. Imaging analysis will focus on connectivity within threat-related regions including the amygdala and salience network, and reward/motivational- related fronto-striatal circuits, including the nucleus accumbens and medial/ventromedial prefrontal cortex.

We will evaluate whether participation in WHEEL reduces abnormal connectivity in threat-responsive regions and enhances connectivity within reward/motivation-related circuits. By integrating brain imaging, clinical data, and patient experiences, this work seeks to uncover the biological and psychological mechanisms that contribute to chronic pain and pain amplification in SLE. Ultimately, the findings may guide future therapeutic approaches aimed at improving quality of life for individuals with SLE.