The Oklahoma Study of Native American Pain Risk: Stress and Resilience Mechanisms - 07. Project Summary/Abstract This proposal will explore the impact of a societal-level stressor and cultural resilience on Native American (NA) chronic pain risk mechanisms. NAs experience higher rates of chronic pain than the general U.S. population and we have shown that pain-free NAs are ~3x more likely than non-Hispanic Whites (NHWs) to prospectively develop chronic pain. Our work over the past decade has identified several stress-related factors (unfair treatment, psychological stress, somatic threat sensitivity, cardiometabolic allostatic load) that work collectively to promote a unique NA pain risk phenotype we call “silent” spinal sensitization (sensitization of spinal pain neurons without sensitization of pain experience). This discovery represents a paradigm shift in how NA pain risk is conceptualized because it is not detectible by pain self-report. As a result of European settlement, NAs were made to redefine their relationship with the Earth, including forced removal from sacred lands. Moreover, current NA lands are often targets of waste disposal, pollution, and hazards. The traditional NA worldview involves an intimate relationship with the land in which all of nature is interconnected. Within this worldview, nature degradation is akin to desecration of the body/soul. This proposal will demonstrate the impact of a societal-level stressor (nature degradation) on NA chronic pain risk mechanisms (Aim 1). A latent nature degradation variable will be created and linked to participants via geocoding. Our preliminary work shows this variable: a) explains 87% of the variance in the original variables, b) correlates with the proportion of NAs within a census region suggesting it assesses NA exposure to nature degradation, and c) promotes silent spinal sensitization in NAs, but not NHWs. However, these pilot data must be replicated to address limitations. Our study will model silent spinal sensitization using state-of-the art methods to assess central sensitization, endogenous pain inhibition, and subjective pain experience. Physiological markers of spinal (nociceptive flexion reflex) and supraspinal (pain-evoked cortical potentials) pain processing will be used to verify the level of the neuraxis where sensitization occurs. Allostatic load (stress-related wear-and-tear on physiological systems) will be comprehensively assessed from multiple systems, including neuroendocrine and cardiovascular responses to psychosocial stress. To address the lack of research on NA pain resiliency, we will determine if cultural connectedness (NA-specific cultural resilience) buffers against NA chronic pain risk mechanisms (Aim2). Results will a) address an understudied health concern in NAs, b) help guide policy decisions to reduce NA pain risk, c) support a paradigm shift in how NA pain risk is conceptualized, d) identify targetable mechanisms to inform a precision medicine approach to prevent NA pain and disability, and e) identify resiliency factors to reduce the impact of NA chronic pain risk mechanisms. This community engaged research involves input from NA community partners (Indigenous Advisory Council, tribal IRBs) in the design, execution, and dissemination of the work.