Ethnic disparities in pain processing among healthy adults: μ-opioid receptor binding potential as a putative mechanism

Abstract

Although ethnic differences in pain perception are well documented, the underlying mechanism for these outcomes has not been established. µ-opioid receptor (MOR) function might contribute to this disparity, given that MORs play a key role in pain sensitivity and modulation. However, no study has characterized ethnic differences in MOR physiology. This study sought to address this knowledge gap by examining differences in µ-selective agonist binding potential (BPND; [11C]-Carfentanil) between 27 non-Hispanic black (NHB) and 27 demographically similar, non-Hispanic white participants. Participants completed questionnaires and two 90-minute high-resolution research tomograph positron emission tomography (PET) imaging sessions. During PET imaging, a capsaicin or control cream was applied to individuals' arms, and pain ratings were collected. Bonferroni-corrected PET volumes of interest analyses revealed significantly greater [11C]-Carfentanil BPND among NHB participants in bilateral ventral striatum ([left]: F1,52 = 16.38, P < 0.001; [right]: F1,52 = 21.76, P < 0.001), bilateral dorsolateral prefrontal cortex ([left] F1,52 = 17.3, P < 0.001; [right]: F1,52 = 14.17, P < 0.001), bilateral subgenual anterior cingulate cortex ([left]: F1,52 = 10.4, P = 0.002; [right]: F1,52 = 12.91, P = 0.001), and right insula (F1,52 = 11.0, P = 0.002). However, there were no significant main effects of condition or ethnicity × condition interaction effects across models, likely attributable to individual variability in the direction of change within groups. BPND values were significantly correlated with pain ratings collected during the capsaicin condition (r range = 0.34-0.46, P range = 0.01-0.001). Results suggest that NHB individuals might have generally greater unoccupied MOR density than non-Hispanic white peers. Findings have implications for physiological differences underlying ethnicity-related pain disparities. If replicated, these results further emphasize the need for tailored treatments in historically underserved populations.

Confronting Racism in All Forms of Pain Research: Reframing Study Designs

“…To illustrate this shift in study design related to pain, we re-analyzed our (Letzen, CM Campbell) published data reporting differences between healthy Black and NHW adults in μopioid receptor binding potential during the experience of noxious stimuli 85 . Although this project was one of the first to examine physiological pathways of heightened pain sensitivity (on average) among Black adults, it could not identify why differences emerged (i.e., "the causes of the causes").…”

A social affective neuroscience lens on placebo analgesia

“…Across multiple studies, perceived similarity is associated with stronger placebo analgesia [58,133] and lower expected pain [55], whereas greater experienced discrimination has been linked to higher pain and stronger brain responses to pain in Black/African American participants in a study of acute pain [128]. Non-Hispanic Black participants have also been shown to exhibit reduced MOR binding during painful stimulation [134], which might contribute to these effects. Placebo researchers and health disparities researchers should work together to understand how placebo and nocebo effects might differ across sociocultural groups, while taking a cultural neuroscience perspective into account [135].…”

Resilience, pain, and the brain: Relationships differ by sociodemographics

“…Clinically relevant differences are most apparent for the NHB women (Table 5). Our findings contribute to a growing body of evidence, which will help further inform interpretations of ethnic/race group differences in clinical and experimental pain and identify potential targets to reduce health disparities and improve chronic pain prevention strategies (Campbell & Edwards, 2012;Kim et al, 2019;Letzen et al, 2020;Losin et al, 2020).…”