Ethnic differences in endogenous pain regulation: PET imaging of opioid receptors

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DESCRIPTION (provided by applicant): Chronic pain is the number one motivator for healthcare utilization, affects over 100 million Americans, costs in excess of one trillion dollars annually and exacts profound suffering and physical disability. Considerable evidence has demonstrated that ethnic groups show substantial variability in the experience of acute and clinical pain, with African Americans (AAs) having increased prevalence of a number of clinical pain conditions and reporting higher levels of pain severity and pain-related disability in response to pain when compared to non-Hispanic whites (NHW). Evidence suggests that disparities between these groups are independent of other demographic factors such as age, sex, socioeconomic status, education, employment, marital status, and other potential confounders, such as medical comorbidities and disease duration. These ethnic differences have been mirrored in the laboratory where controlled, systematic noxious stimuli are applied to healthy individuals. Ethnic differences in laboratory pain responses are well-established, suggesting increased sensitivity to noxious stimulation among AAs compared to NHWs. In our previous work, we have demonstrated enhanced responsiveness in AAs to noxious stimulation on several tasks that indirectly assess endogenous pain-inhibitory systems that are at least partially opioid-mediated. Ethnic differences in endogenous opioid neurotransmitters in the central and peripheral nervous system suggest that these systems function less efficiently among AAs and may account for a substantial proportion of the ethnic differences observed in pain and analgesic responses. In addition, pharmacogenetic research shows substantial ethnic group differences in the metabolism, clinical effectiveness, and side-effect profiles of many drugs; including analgesics. The overwhelming majority of clinically used opioids elicit their effects through activation of the mu-opioid receptor, making it an extremely relevant target for investigation. We propose to examine ethnic differences in the supraspinal endogenous opioid system using positron emission tomography (PET) imaging of mu-opioid receptors employing the mu-selective agonist [11C] carfentanil. Healthy AAs and sex, age, SES matched, NHW participants will undergo one baseline (non-pain) and one capsaicin-induced pain PET session using [11C] carfentanil. The current proposal will measure mu-opioid binding potential and examine its role in ethnic group differences in pain sensitivity. Our overarching objective is to investigate the endogenous opioid system as the mechanism underlying the association between ethnicity and pain sensitivity, thereby enhancing our understanding of the neurobiology of ethnic differences. These findings will have far reaching implications; including elucidating a tangible, physiological mechanism underlying ethnic differences in pain, for prescribing analgesics and advancing personalized medicine. Enhancing our understanding of mechanisms underlying ethnic differences in pain is likely to assist in the refinement of targeted interventios to alleviate clinical pain in at-risk populations, and aid in reducing pain-related health disparites.