Understanding pain embodiment and opioid misuse risk in chronic pain using neuroimaging

PROJECT ABSTRACT The opioid crisis remains an ongoing public health concern as annual deaths due to opioid overdose remain at record-high levels. Chronic pain contributes to both non-fatal and fatal opioid overdoses, and the lack of effective and safe non-opioid options for long-term pain management is a significant barrier to the treatment of substance use disorders. There is an urgent need to better understand the factors linking co-occurring pain and substance use to poor functional outcomes, such as overdose and pain-related suicidality. Both the sensory and affective components of chronic pain are essential to consider as both contribute to the process of pain embodiment. Pain embodiment is a part of the chronic pain experience that is characterized by a tendency to apprise bodily sensations as a threat to bodily integrity. Chronic pain patients with high pain embodiment may experience more pain-related anxiety and may be more motivated to use opioids as a safety-seeking behavior to escape pain- related distress. Here, we propose to characterize pain embodiment and how it relates to risk for opioid misuse and brain network changes as measured by resting-state functional magnetic resonance imaging (fMRI). We will study healthy individuals, individuals with chronic pain, and individuals recovered from chronic pain with a state- of-the-art imaging protocol and a comprehensive set of pain and clinical measures. Our central hypothesis is that, in chronic pain, pain embodiment increases the risk for opioid misuse and that this relationship is reflected in networks shared by addiction and central pain processing: the default mode network (DMN) and the salience network (SN). Aim 1 will identify concepts of pain embodiment that relate to opioid misuse risk. Aim 2 will determine how pain embodiment and opioid misuse risk are reflected in functional connectivity changes in the DMN and SN. Aim 3 will determine how pain embodiment and opioid misuse risk influence concentrations of proton brain metabolites in the anterior cingulate cortex, a major hub of the SN. Together, this proposal will illuminate how pain embodiment is reflected by changes in central pain processing and offer novel insights into the mechanisms contributing to poor functional outcomes in co-occurring chronic pain and opioid misuse. An interdisciplinary team of mentors will provide training in clinical and psychological behavioral measures regarding chronic pain as well as training in magnetic resonance imaging methods, including acquisition and data analysis. This training will be complemented by clinical mentorship in psychology and physical medicine and rehabilitation. This training plan was developed in collaboration with my Sponsor and Co-Sponsor to complete the central goals of conducting independent, collaborative research; advancing communication and grant-writing skills; effectively mentoring and teaching trainees in a supportive environment; and honing clinical skills in preparation for the return to medical school. This training is ideal for a future physician-scientist with the goal of improving patient care at the intersection of translational research and the clinical management of co- occurring substance use disorders and chronic pain conditions.