Modifiable Mechanisms Linking Chronic Pain to Suicide Risk - ABSTRACT Suicide is a critical public health issue and a leading cause of death in the United States. Individuals living with chronic pain face more than double the suicide risk compared to the general population. Despite this elevated risk, the mechanisms linking chronic pain to suicide remain unclear, and there are no established, targeted suicide prevention strategies for this growing and underserved population. The Catastrophizing, Anxiety, Negative Urgency, and Expectancy (CANUE) model offers an innovative framework for understanding suicide risk in the context of chronic pain. Originally developed to explain substance use vulnerability, CANUE posits that pain promotes maladaptive coping through negative reinforcement, and that cognitive-affective vulnerabilities—such as intolerance of uncertainty (IU) and anxiety sensitivity (AS)—amplify distress and motivate escape-based behaviors like suicide. IU reflects aversion to ambiguity, while AS reflects fear of anxiety- related bodily sensations. Both are theorized to heighten emotional reactivity to pain and fuel the desire for relief, including suicidal thoughts and urges. However, no study has directly tested this model in the context of chronic pain and suicide risk. The goal of this R21 study is to generate novel empirical data to determine how IU and AS interact to shape pain-related distress and momentary suicide risk using an innovative, multimodal research design. We will recruit 90 adults with chronic musculoskeletal pain and elevated suicide risk. Participants will complete a comprehensive laboratory session that includes validated self-report and behavioral tasks assessing IU, AS, and other CANUE-related factors, as well as quantitative sensory testing (QST) to assess pain sensitivity and affective responses to pain in a controlled setting. Immediately following the lab session, participants will complete a 21-day ecological momentary assessment (EMA) protocol, delivering a mix of time-based, random, and event-based mobile surveys to assess fluctuations in pain, pain-related affect, suicidal ideation, and escape- motivated thoughts in real time and natural environments. This combination of experimental and real-world methods will allow for the first rigorous test of whether IU and AS have unique and interactive effects on pain sensitivity, pain-related affect, and recent suicidal ideation in the lab (Aim 1), and whether they moderate the dynamic, moment-to-moment associations between pain, affect, and suicide risk in daily life (Aim 2). We hypothesize that participants with higher levels of IU and AS will report greater recent suicidal ideation severity and show greater pain-related negative affect in response to experimental pain. We also anticipate that IU and AS will moderate real-time links between pain and suicidal ideation in the natural environment. By leveraging laboratory and ecological data, this project represents a significant and innovative step forward in understanding the mechanisms underlying suicide risk in chronic pain. Findings will advance theoretical models of suicide and pave the way for more personalized, mechanistically informed prevention strategies for this high-risk and understudied population.
