07. Project Summary/Abstract This proposal will explore the role of structural racism and discrimination (SRD) in the Native American (NA) chronic pain disparity. 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 factors (discrimination, 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. NAs have suffered generations of SRD due to colonization (eg, genocide, cultural oppression), including forced removal from sacred lands and policies that lead to desecration of their environment. The traditional NA worldview involves an intimate relationship with the environment in which all of nature is interconnected. Within this worldview, environmental desecration is akin to desecration of the body/soul. This proposal will demonstrate the impact of environmental SRD (racialized distribution of environmental pollutions/hazards) on mechanisms of the NA pain disparity (Aim 1). The EPA's 11 environmental (in)justice variables will be leveraged to form a societal-level latent variable representing Racialized Environmental Desecration that will be linked to participants via geocoding. Our preliminary work shows this variable: a) explains 87% of the variance in the original 11 variables, b) correlates with the proportion of NAs within a census region suggesting it assesses racialized NA exposure to pollution, 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 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 a NA-specific resource (ie, cultural connectedness) buffers against SRD and its negative consequences (Aim2). Results will a) address an understudied health disparity in an underserved population, b) help guide policy decisions to reduce the NA pain disparity, c) support a paradigm shift in how NA pain risk is conceptualized, d) identify targetable mechanisms to inform a precision medicine a...