2.3.2 The role of racial-ethnic disparities
Barnett and colleagues used 2016-2019 Medicare claims data to identify racial-ethnic differences in the prescription and rates of use of medications to treat OUD (buprenorphine, intramuscular extended-release naltrexone) and prevent opioid overdose deaths (naloxone), as well as high-risk prescription medications (e.g., opioid analgesics and benzodiazepines)69. They found that Black persons are less likely to access buprenorphine and naloxone than non-Hispanic White (NHW) populations. This is particularly concerning, in that Black persons have experienced greater increases in opioid-involved overdose deaths than any other racial group, growing by a factor of 7.7 between 2010 and 202070.
Noted disparities in OUD treatment are mirrored by disparities in chronic pain treatment in minoritized patients living with OUD. Black and, to a degree, Hispanic adults have been shown to experience greater clinical pain severity and pain-related disability than NHW adults71-73. In laboratory models of pain, Black persons have been found to exhibit lower pain thresholds and lower tolerance of pain74-80. Growing evidence highlights that these racial differences in pain perception may result from the harmful effects of health-care disparities and societal racism in general.
At the mechanistic level, racism-related stress, or pervasive emotional distress caused by racial discrimination, may negatively affect pain perception through sleep disturbance and corticolimbic disfunction, as demonstrated by Letzen and colleagues81. The authors assessed the effects of race-related stress on the corticolimbic system, using positron emission tomography (PET) to evaluate the binding potential of ยต-opioid receptors; actigraphy sleep variables were also measured81. An association was demonstrated between levels of exposure to racism and pain sensitivity through mechanisms of: (1) race-related stress, (2) sleep disturbances associated with race-related vigilance, and (3) corticolimbic opioid-receptor modulation changes. These findings emphasize the role of multi-disciplinary trauma-informed approach to pain treatment in racialized populations, as the experience of racism may worsen the experience of pain and be evident beyond physical domains82.
In summary, biological, psychological, and social factors converge to impact the experience of chronic pain, challenging holistic pain assessments. For persons with OUD, this assessment is further complicated by opioid-related disruptions of pain pathways. For optimal clinical outcomes, it is imperative to undertake a comprehensive, multidisciplinary pain evaluation that can account for this complexity (Figure 1 ).
SPECIAL CONSIDERATIONS
Tolerance and hyperalgesia
Pain assessment in individuals with OUD can be complicated by the phenomena of tolerance and hyperalgesia, which are opioid-induced changes to pain systems that can result in increased analgesic demand by persons with pain26. Tolerance is characterized by a decreased response to an opioid over repeated administration, necessitating dose increases to achieve the previous magnitude of analgesic effects26. Opioid-induced hyperalgesia (OIH) is a paradoxical state of heightened pain sensitivity that is distinct from and superimposed on the painful condition26, 83. As people with chronic pain continue to deteriorate, increasing need for opioids at higher doses can indicate several diagnostic hypotheses. First, it may reflect untreated or inadequately treated pain that could indeed benefit from higher dose adjustments84, 85; second, it may signal the development of tolerance to the analgesic effects of the current opioid regimen86, 87; or third and alternatively, the dose escalation itself may be triggering OIH, in which case higher doses might, in fact, be detrimental26, 83.
Multiple mechanisms likely underlie the development of tolerance and OIH. In some ways similar to mechanisms for pain chronification, these include NMDA-receptor activation, neuroadaptations in descending pain modulatory pathways, increased excitatory neuropeptides, and glial cell activation85, 87, 88. However, the precise etiology remains incompletely understood. Clinically, distinguishing between under-treated pain, tolerance to analgesic effects of opioids, and hyperalgesia is crucial yet challenging in persons with OUD. A comprehensive phenotyping of the pain experience exploring characteristics, timing, triggers, and radiation can determine if pain represents disease progression or an opioid-related effect. A trial of opioid dose reduction may also clarify if OIH is present87. Carefully weighing these pain-related factors helps clinicians to identify the source(s) of pain and optimize pain management in this complex clinical population.