Chronic musculoskeletal pain is a highly prevalent, debilitating condition with a paucity of effective treatments. Usually starting in midlife, it persists into late years, with up to 50% of people over 65 reporting persistent pain. Patients futilely attempt numerous treatments, including risky surgeries to alleviate pain. Recent studies suggest that the central nervous system- i.e., aberrantly functioning brain circuits -plays a role in the origin and maintenance of chronic pain. However, the specific mechanisms underlying central chronic pain are not yet fully understood. The PI of this project formulated evidence-based Developmental Theory of predisposition to central chronic pain. Insights from translational neuroscience suggest that pain and feelings of interpersonal rejection or abandonment share neural circuits, neurotransmitters, genetic and immune markers, and that interpersonal emotion regulation between child and caregivers is crucial for the optimal development of this shared system. Early interpersonal adversity may lead to its aberrant development causing increased sensitivity to pain and interpersonal distress, and difficulty down-regulating and differentiating between them, thus creating a vicious cycle of pain and interpersonal suffering, predisposing to chronic pain in later years. In fact, early interpersonal adversity and adult heightened rejection sensitivity and loneliness are highly prevalent among chronic pain patients. To study the neural bases of these phenomena, the PI developed a novel brain imaging (fMRI) paradigm that measures the extent of modulation of pain by feelings of rejection. Her preliminary studies suggest that (a) feelings of interpersonal rejection modulate pain on a neural level among healthy people, (b) this neural modulation is associated early interpersonal adversity, and (c) non-optimal early interpersonal environment is associated with increased pain sensitivity in adulthood in an animal model. The proposed study will investigate the neural mechanisms underlying effects of early interpersonal adversity and mid-life interpersonal distress on central pain processing among patients with chronic pain. Low back pain is a highly common pain problem and 20-40% of back surgeries for pain result in chronic post-operative pain (CPOP). Using CPOP as a model to differentiate between central nervous system vs structural spine factors contributing to low back pain, pre-surgery brain imaging fMRI scans will be used to study predisposition to CPOP among patients with varying levels of early interpersonal adversity and current interpersonal distress. This will be the first study to (a) investigate the specific effects of early life and adult interpersonal adversity on neural circuits underlying pain and (b) use brain imaging to predict CPOP. This award will also measurably advance the training of PI in aging research methodology and translational social affective neuroscience, and will launch her translational research program which aims at identifying targets for reversing the drastic effects of interpersonal adversity on chronic pain and health, and for development of prevention programs for this problem of significant public health importance.
Chronic musculoskeletal pain is a highly prevalent, debilitating condition with insufficiently effective treatments - an alarming public health problem. Usually starting in midlife, it persists into late years, often with no relief. This research study will investigate the central neural mechanisms underlying chronic pain and the mechanisms by which the early interpersonal adversity alters brain circuits predisposing a person to chronic pain later in life. Results will inform the development of new targeted treatments for chronic pain in mid- and late-life aimed at improvement of the pain neural circuits functioning by reversing the effects of early interpersonal adversity, thus having a significant public heath impact.
