Immunologic Response to Negative Cognition in Persons With Chronic Pain

Principal Investigator/Program Director (Last, First, Middle): Darnall, Beth APS Future Leaders in Pain Small Research Grants Application Page 5 Continuation Format Page

Summary: Chronic pain is stressful, both physically and psychologically. Stressful experiences induce autonomic nervous system arousal, which reliably leads to inflammation and immune suppression. Inflammation then exacerbates existing pain and may be a key factor in both the genesis and maintenance of pain. Stress-induced immune effects are detected two hours (2 hrs) post-stressor, suggesting only a few stressful experiences per day may be sufficient to sustain elevated pain levels1. Cognition has emerged as a potential mediating factor in the relationship between pain and stress. Mentally recreating an emotionally stressful event induces de novo physiological stress1. In other words, thinking about an emotionally charged event down-regulates autonomic stress responses and subsequent immune effects. Therefore, exploring cognition as a mediating factor between stress, pain, and inflammation will inform our understanding of pain pathways, as well as improve treatment for pain.

Study Rationale: The acute stress response induces immunosuppression; however, this relationship has been studied in arbitrary models only (shock avoidance, job interview). This study employs the novel approach of examining stress and immune responses to a personally relevant stressor (pain); prior studies used arbitrary models only (shock avoidance, job interview). Pain offers a highly salient and personal context well-suited for investigation of negative cognitive perseveration. Pain is acutely sensitive to exacerbation via inflammation, and thus the relevance of examining immune effects of rumination on future negative expectations ("expecting the worst") is underscored.

Goal: To test the biological consequences of negative expectations, achieved via an active 10-minute negative cognitive perseveration on a personally relevant stressor: future worsening of one's chronic pain condition. Biological stress response will be measured via heart rate (HR), blood pressure (BP) and serum cortisol. Impact of negative cognition on inflammation will be measured using interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) as biomarkers of immune function, controlling for depression and pain catastrophizing. This study aims to inform the understanding of pain mechanisms.

Aim 1: Determine the magnitude of an autonomic stress response to an induction of negative cognition.

Aim 2: Determine immune effects of the experiment-induced stress response.

Aim 3: Establish whether a pre-existing tendency to catastrophize mediates the relationship between experiment-induced negative perseveration and immune effects.

Aim 4: Establish whether stress-related increases in IL-6 remain elevated post 2 hrs.