16th Annual NIH Pain Consortium Symposium on Advances in Pain Research

Pain and Pandemics: Challenges and Opportunities in the Current Social and Healthcare Climate

May 24 and 25, 2021

All-Virtual Meeting—Zoom Event

 

Acronym Definitions

Meeting Summary

Introduction

The National Institutes of Health (NIH) Pain Consortium, established in 2003 to foster collaboration among NIH Institutes and Centers involved in pain research, held its 16th Annual Symposium on May 24 and 25, 2021. This year, the Symposium was again held as a virtual meeting because of the ongoing COVID-19 pandemic. Opened by Dr. Walter Koroshetz, Director of the National Institute of Neurological Disorders and Stroke (NINDS), the Symposium convened various stakeholders to survey the landscape of recent advances in pain research and treatment, and to discuss the prospects of ongoing and future research efforts to improve pain care and reduce racial and ethnic pain care disparities.

The Symposium featured two keynote addresses. Dr. Julie Fritz of the University of Utah discussed the concept of epidemics and the interaction among the current epidemics of pain, health inequities, and COVID-19. Dr. Robert Malenka presented on neural mechanisms of prosocial behavior and the social transfer of pain. Panel sessions focused on the social determinants of health and chronic pain, the impacts of the COVID-19 pandemic on pain care and management, and interventions for pain care disparities.  

Participants heard testimonials from Lt. Aaron Banas, a pain patient suffering from long COVID, and Ms. Norma Guzman, a pain patient suffering from the sequelae of injuries sustained in a car accident. Finally, the Symposium featured presentations by Ms. Daisy Cantu, this year’s Mitchell Max Awardee, and by junior investigators who were also nominated for the prize.

Appendices A, B, and C contain the 2021 NIH Pain Consortium Symposium agenda, presenter biographies, and junior investigator names and abstract titles, respectively.

Welcome and Opening Remarks

Walter Koroshetz, MD; Director, NINDS, Pain Consortium Executive Committee Chair

The mission of the NIH Pain Consortium is to enhance pain research and promote collaboration among researchers across all NIH Institutes and Centers that have programs and activities related to pain. Among the topics the Pain Consortium confront are the pain and opioid misuse epidemics, both of which intersect with the ongoing COVID-19 pandemic.

All three epidemics disproportionately affect certain populations, including women, older people, and people of lower socioeconomic status and educational attainment. Notably, Black Americans, American Indians, Latinx Americans, and Asian Americans all exhibit higher rates of chronic pain than do white Americans. Racial and ethnic minorities have also experienced a disproportionate burden from COVID-19. The 16th Annual Pain Consortium Symposium convened to discuss the forces underlying these disparities, exploring their historical and modern causes as well as potential strategies to end them.

Keynote Address: Pain Management in a Time of Dual Pandemics: Opportunities to Advance Health Equity

Julie M. Fritz, PT, PhD, FAPTA; University of Utah

Dr. Fritz explored the term “epidemic” as applied to pain, opioid abuse, and health care disparities. People choose to define an ongoing phenomenon as an epidemic because strong social pressures make the status quo no longer tolerable and create a sense of urgency to act. For pain and opioid abuse, urgency grew over the previous decade, culminating in the launch of the HEAL Initiative to address the widespread opioid addiction within the United States. Similarly, the need to address health care disparities and health inequities has increasingly drawn attention during the past several decades—Congress commissioned a landmark document titled Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care in 1999 to examine and document these issues. Unequal Treatment reported that health care disparities arise from structural racism as well as the biases, prejudices, and stigma of actors in the health care system. However, although the sense of urgency to adress the problem has grown, the point at which transformative change occurs has yet to be reached. Disparate access to pain management, alongside other societal factors, intensifies the effects of chronic pain in social groups defined not only by race and ethnicity, but also by veteran status, rural living, low educational attainment, and/or poverty. However, racial and ethnic minorities are particularly affected by the prejudice and bias of health care providers.

COVID-19, the world’s most recently recognized epidemic, has been characterized by many of the same racial and ethnic inequities that structure the epidemic of pain. Moreover, the COVID-19 pandemic has exacerbated the pre-existing epidemics of health disparities, pain, and opioid abuse. Since the onset of the pandemic in the United States, opioid overdose deaths have increased, peaked, and not yet returned to pre-pandemic levels. These overdose deaths spiked despite an early decrease in opioid prescription writing that has since returned to pre-pandemic levels. Chronic pain patients have reported disruptions or halts to non-pharmacologic pain treatment, such as behavioral health treatments, physical therapy, and complementary and integrative health care, during the pandemic. Further, the stressors associated with the pandemic, and the response to it, have worsened pain symptoms. These issues have affected social groups differently—with disadvantaged communities bearing a disproportionate burden of COVID-19.

Social determinants of health influence the efficacy of the wide variety of strategies employed to meet the challenges posed by the COVID-19 pandemic. A pre-pandemic RAND survey regarding telehealth delivery suggested that most individuals had participated in a form of telehealth—typically, email through a patient portal. However, only 4 percent had used video conferencing, and patient attitudes toward the practice varied. Patients with lower educational attainment or income, older patients, and Black patients were less likely to report an interest in videoconferencing for health consultations. Early in the pandemic, the use of telehealth services expanded and 46 percent of completed telehealth visits occurred through video conferencing, but the extent depended on age, gender, race, native language, ethnicity, and rural vs. urban living. In addition, patients’ likelihood of using videoconferencing differed according to the type of health care service received; for example, patients receiving behavioral health services used the delivery modality more frequently than patients receiving specialized services such as rehabilitation. Dr. Fritz cautioned that unless researchers and clinicians intentionally combat existing health disparities, they are likely to exacerbate them in their telehealth practices. 

Epidemics typically end in one of two ways: by recessing into the societal background at a level deemed acceptable or by simply being forgotten. Researchers must intentionally work to limit health inequities and remain vigilant for reemergence of this epidemic so that it ends by recessing. Development of transformative approaches to mitigation and management of inequities in pain management, which will be discussed during the Symposium, will be central to that work.

Keynote Speaker Q&A

Importance of Metaphor

Dr. Fritz suggested that using the term “epidemic” rather than “war on” (e.g., war on opioids) is useful because the connotations of those metaphors differ substantially. For example, epidemics are mitigated, whereas wars eliminate enemies. In the cases of pain management and opioid use, total elimination is impossible, and therefore those epidemics must be approached with mitigation strategies. Although the medical and scientific communities should intend to eliminate health care disparities, they must remain vigilant for reemergence and not assume that elimination occurred and is permanent.

COVID-19-Related Health Care Disruptions

Dr. Fritz noted that services and appointments for chronic pain patients were disrupted by a combination of circumstances during the COVID-19 pandemic: policy changes by health care systems, providers’ rapid and imperfect responses to those changes, and reasonable health concerns of both patients and providers. Some interventions requiring touch (e.g., chiropractic, physical therapy, acupuncture) are very difficult to adapt to telehealth, and researchers must consider potential hybrid models that leverage advantages of face-to-face interventions while using technology to extend those services and increase access.

Panel Session: The Impact of Social Determinants of Health on Chronic Pain and Pain Management

Moderator: Laura Wandner, PhD; National Institute of Neurological Disorders and Stroke

The Unequal Burdens and Unheard Voices of Pain: Causes and Consequences

Carmen R. Green, MD; University of Michigan, Ann Arbor

Dr. Green discussed historical perspectives on social determinants of health as well as how those determinants will shape the future of medicine and society. She described social determinants of health as where people work, live, play, or pray, and noted that disparities in those places cause some people to have shorter lifespans.

Such modern medical disparities, particularly those impacting Black people, are founded in the history of United States. Many regard the Tuskegee Syphilis Study as the preeminent example of medical abuse as well as the foundation of Black mistrust in the U.S. medical system; however, the history runs far deeper. Benjamin Rush, a signer of the Declaration of Independence, abolitionist, owner of enslaved people, and so-called “father of American psychiatry,” believed that Black skin was a disease. Samuel Cartwright, a then-well-regarded physician of the mid-19th century, defined “drapetomania” as a psychiatric disease of enslaved Black people that caused a desire for freedom and was treated by beating the affected individual. Drapetomania persisted in medical dictionaries until at least 1914, half a century after the end of slavery in the United States. Dr. Crawford Long, the first person to administer ether in the United States, and J. Marion Sims, considered the father of gynecology, performed intentionally painful experiments on enslaved children and women. In the 20th century, Henrietta Lacks was treated for cervical cancer in the only hospital near her home that would treat Black patients and became the unwitting donor of the first and still most widely used immortal cell line, from which her physicians profited.

This history has developed into structural racism in medical settings, where African Americans are sometimes viewed as threats to be managed rather than patients to be treated. For example, Dr. Green’s team studied contemporary security interactions in hospitals and found that hospital security was summoned to confront Black patients and their visitors 2.4 to 2.7 times more often than white patients and their visitors. Furthermore, while high socioeconomic status correlated with fewer security interactions for white individuals, security confronted Black individuals consistently regardless of wealth. This imbalance is reflected across social and medical disparities.

Racial and ethnic minorities experience accelerated aging, and age is associated with increased pain conditions. People of color, older people, and women all report higher prevalence of chronically painful conditions and are less likely to receive adequate analgesic treatment than white patients, younger patients, and male patients. Unsupported beliefs that racial minorities are at greater risk of addiction than white people contribute to this inadequate analgesia. Pain has many physical, social, and emotional consequences, and how those consequences intersect with racial or ethnic minority status remains unexamined. In addition, Dr. Green suggested that pain stories are deemed “just” or not by both individuals and society; a veteran’s pain may be more respected than that of a prisoner.

Today, the United States is confronting its history and grappling with its persistent racial disparities. In 1997, President Bill Clinton issued an apology for the Tuskegee experiments, and the American Medical Association apologized in 2008 for segregation and restriction of minority physicians. In March 2021, Dr. Francis Collins apologized for structural racism within the NIH grant review processes. The same week, however, the Journal of the American Medical Association (JAMA) issued a statement that no structural racism in medicine exists. Dr. Green suggested although while awareness of implicit bias, discrimination, and racism has generally increased, the process of truly confronting these issues has only begun, as exemplified by JAMA’s statement. She stated that managing these problems begins with meaningful apologies associated with action to remediate the injustices perpetrated by a given institution.

Discrimination as a Social Determinant of Pain

Vani A. Mathur, PhD; Texas A&M University

Discrimination is now broadly recognized as a social determinant of health and is one mechanism by which cultural “-isms”, including racism, sexism, heterosexism, gender binarism, and ableism, shape patterns of health and disease along socially created demarcations to produce health disparities. Discrimination is defined as the unjust or prejudicial treatment of a person or group based on some aspect of observable or assumed identity. It is perpetrated by individuals and social institutions and serves to create and maintain systems of unequal power, favoring dominant social groups and disadvantaging minoritized groups. Discrimination in the United States occurs across domains of life and is associated with disparities and lived experiences; for example, where people live and grow, how others treat them, and the opportunities and quality of resources available to them.

In clinical settings, Americans with stigmatized identities experience pervasive discrimination. For example, 32 to 57 percent of Black Americans experience discrimination from their medical providers. Twenty percent of Latinx Americans and 33-41 percent of transgender Americans report the same experience. Discrimination frequently manifests as disbelief, disregard, and suspicion, burdening patients with proving themselves or their pain and resulting in increased suffering. Discrimination in the context of pain management is associated with increased likelihood of unmanaged and persistent pain, as well as greater severity of chronic pain. Experiences of discrimination in clinical settings are also associated with increased laboratory pain measures.

Dr. Mathur’s team examined experiences of discrimination among people with sickle cell disease, who are disproportionately Black and who frequently face both race- and disease-based discrimination from their health care providers, especially when presenting with severe pain. Thirty-eight percent of study participants reported experiencing discrimination from their doctors, as well as greater clinical pain severity and pain-induced disability. In addition, when subjected to pain testing in laboratory settings, participants exhibited no significant difference between heat pain thresholds or tolerances based on reported discrimination. However, those who reported discrimination in health care settings perceived supra-threshold temperatures as more painful and more unpleasant than those who did not report discrimination; they also experienced greater pain persistence after heat pain tests. Furthermore, that same subset of patients who reported discrimination exhibited greater temporal summation of mechanical pain, considered a marker of central sensitization, providing more insight into the mechanism of the discrimination-pain relationship. Discrimination remained a significant predictor of temporal summation, although not the other laboratory measures, even after controlling for severity of clinical pain. Together, these findings indicate a synergy of suffering from pain and encounters people have while seeking pain care.

Dr. Mathur’s team has also studied how Latinx Americans experience discrimination and how these experiences interact with experiences of pain. As part of the study, participants completed a survey in which they could report on scales including exclusion, stigmatization, workplace or educational discrimination, and overt violence, threats, and aggression. Ninety-four percent of participants reported experiencing race-based discrimination, which again was associated with increased temporal summation among Latinx Americans without chronic pain, further supporting an association between discrimination and sub-clinical pain sensitization.

Discrimination in both health care settings and in general remains an understudied and underacknowledged determinant of pain. Ahistorical and acontextual examinations of pain disparities likely miss important causal factors and lead to shortsighted interpretation of existing disparities. Current knowledge is limited by the lack of appropriate metrics, as well as the lack of diversity in research. Existing research has largely focused on interpersonal discrimination; however, most interpersonal discrimination is fueled, permitted, and replicated by structures, systems, and practices that reinforce discriminatory treatment. Dr. Mathur suggested that interventions to remediate discrimination must focus not on individuals, but on those systems and structures.

Optimizing Pediatric Pain Management via Health Technology and Participatory Research Approaches

Michelle Fortier, PhD; University of California, Irvine

Study of pain function and management in pediatric populations is frequently neglected, requiring potentially inaccurate extrapolations from adult pain research. Many providers lack the knowledge to properly assess and manage pain in children, resulting in improper pain treatment. Moreover, parents and children often hesitate to report pain, especially in the oncology setting, because parents fear side effects and children fear reifying their pain by reporting it and losing their ability to participate in social activities or see friends. In addition, pain treatment strategies beyond pharmaceuticals, such as behavioral health therapy, can reframe the pain as psychogenic or as a mental illness, making them especially stigmatizing for children.

Pediatric oncology patients now have high survival rates—a great success of medical research.  Pediatric cancer survivors are more likely to experience childhood chronic pain than their peers who never had cancer. While still undergoing treatment, most pediatric oncology patients experience poorly managed pain. Changes in health care delivery have also led to most pediatric oncology patients being treated in an outpatient setting, increasing quality of life but also transferring responsibility for pain management from doctors to parents and caregivers, who frequently respond in ways that unintentionally reinforce pain.

To combat these problems, Dr. Fortier’s team has studied the use of technology to improve access to care and mitigate pain management disparities. The team developed “Pain Buddy,” a web-based app intended for children aged 8 to 18 years that includes a symptom diary remotely monitored by health care providers via built-in alert algorithms, as well as cognitive and behavioral skills training for pain and symptom management. Pain Buddy empowers children to feel in control of their pain and to improve their quality of life during cancer treatment. To encourage continued patient use, Pain Buddy gamifies reporting pain in real time with validated measures. App users can earn virtual currency by using their symptom diaries and implementing coping skills learned in the app. That currency can be used to purchase accessories for their avatars, new avatars, or new backgrounds and themes for the app. The app also incorporates a leveling system using a martial arts theme; as children practice skills, they earn new belts and ultimately receive a black belt. With these built-in inducements, 68 percent of children adhered to diary completion over 8 weeks, reporting enjoyment of the program. Over that 8-week period, children in the intervention group reported significantly fewer moderate-to-severe episodes of pain than children in the control group. To improve the care aspects of the app and further increase treatment adherence, the team plans to tailor the intervention to specific groups of children based on cultural background, language, developmental stage, and other categories.

Dr. Fortier also intends to adapt the app to accommodate Latinx families who are Spanish-speaking and live below the poverty line, a population she regularly encounters at her children’s hospital. Those families experience significantly worse outcomes in both pain and psychosocial outcomes in the oncology setting than the population as a whole. To ameliorate these disparities, the hospital established a community-based participatory research approach and an advisory board of Spanish-speaking parents whose children were treated for cancer. Dr. Fortier’s team is now developing a fully virtual intervention that incorporates culturally competent care, caregiver wellness, and health literacy for Spanish-speaking families in the oncology setting. Dr. Fortier noted that prior literature has shown that technology can both minimize and exacerbate health care disparities; to ensure the former is the result of her app, she relies on the knowledge, expertise, and collaboration of community experts.

Panel Session Q&A

Challenging Structural Injustice

To change the structures that facilitate injustice, Dr. Green suggested that individuals assess their own biases and how discriminatory structures and processes have benefited them. Organizations with historically discriminatory practices should apologize and explain their plans to change moving forward. Regarding biased distribution of opioids, Dr. Green challenged meeting participants to consider whether limiting prescription of opioids has protected people of color from addiction or criminalization, and whether the resulting inadequate pain management experienced by these communities was outweighed by any benefits of those limitations. Dr. Green noted that people of color’s lack of trust in the medical establishment is not without cause and emphasized that physicians take an oath to care for and advocate for any and all patients. Dr. Fortier emphasized the importance of listening to lived experiences and partnering with community experts. Dr. Mathur echoed Dr. Green, particularly reiterating her suggestion to challenge racist assumptions embedded into existing medical beliefs and interventions. She suggested considering targeting racism embedded in social structures including housing and the justice system as extensions of eliminating pain disparities.

Dr. Green noted that disparities exist between treatment choices; for example, people of color have less access to surgeries such as total hip and knee replacement. A multidisciplinary team generally leads to more choices and more effective treatment, but such access to such a team is often blocked for some patients by barriers, such as insurance refusal, that affect people differently based on identity.

Cultural Competence or Humility

Dr. Fortier explained that some aspects of culturally competent care may initially seem counterintuitive; for example, Spanish-speaking families may interpret a provider’s sympathy as hesitancy and asking questions of providers (as authority figures) as disrespectful. Although provider awareness and sensitivity to cultural dynamics is important,  provider trainings do not always translate into measurable behavioral changes. Therefore, an objective of her community partnership work is to empower families to understand the culture of medicine in the United States, in an effort to improve their health literacy.

Dr. Green substituted cultural humility for cultural competency, which emphasizes learning about other cultures by evaluating the self and recognizing one’s limitations to understanding the other culture due to differing lived experiences. She also suggested that physicians should consider themselves to be not only clinicians, but also healers.

Developmental and Cognitive Disabilities

Dr. Fortier discussed children with cognitive and/or social impairments, who have also been neglected in pain research. Artificial intelligence is being developed to enhance pain assessment for developmentally and cognitively disabled children. Current objective observational measures to assess pain in nonverbal children exist often focus solely on the 10-point visual analogue scale rather than functional indications.

A Patient’s Perspective

LT Aaron Banas, PsyD; Walter Reed Hospital

Lt. Aaron Banas relayed his personal experience with long COVID. During late March 2020, Lt. Banas developed symptoms including frequent urination, mild eye pain, and very mild fatigue that progressed to a low-grade fever and severe chills, leading to an emergency room visit and a routine COVID test. The following day, he developed abdominal pain and vomiting and learned that the COVID test returned positive. Lt. Banas quickly developed a myriad of additional symptoms, including persistent and severe headaches, ongoing chills, and body aches. Two weeks after symptom onset, Lt. Banas developed pneumonia and shortness of breath, and was hospitalized.

Four weeks after infection, Lt. Banas still tested positive for COVID and experienced a dramatic symptom shift involving psychiatric and neurological symptoms. Increasing joint and muscle pain inhibited his ability to complete tasks such as climbing stairs. Treatment with carbamazepine addressed many of his most bothersome symptoms, including reducing headache severity and frequency. In mid-July, an electroencephalograph (EEG) revealed no seizure activity, and the carbamazepine was discontinued. Lt. Banas continued to experience many symptoms, including random bouts of inflammation. His pain levels increased through September. A rheumatologist diagnosed fibromyalgia, noting that it could be a COVID symptom. Lt. Banas explained that social stressors, such as political divisiveness and family members refusing to wear masks or receive the SARS-CoV-2 vaccine, exacerbated his pain.

Lt. Banas began micro-current treatment, acupuncture, acupressure, and dietary modifications. These treatments provided greater relief than any other treatment, possibly because of the social connection he developed with those providers during their hour-long sessions. Although he still struggles with joint as well as mid- and lower back pain, Lt. Banas’s symptoms are improving. The abatement of the COVID-19 pandemic likely also helped to relieve his symptoms by relieving stress.

Panel Session: The Impact of COVID-19 and Comorbidities on Chronic Pain and Pain Management

Moderator: Inna Belfer, MD, PhD; NCCIH

The Social Impacts of COVID-19: Risks and Opportunities for Pain and Pain Management

Claire Ashton-James, PhD; University of Sydney

Because pain and pain management are biopsychosocial in nature, the COVID-19 pandemic and associated social changes have had widespread influence on chronic pain. Acute viral infections, including COVID-19, present with myalgia and fatigue, which can persist long after the initial infection resolves. The severity of somatic symptoms during an acute viral infection is correlated with the development of post-viral chronic pain that is both widespread and regional; individuals who survive an illness requiring an ICU admission are at increased risk of long-lasting severe functional limitations and chronic pain. In addition, psychological disturbances, including depression, anxiety, stress, sleep disruption, and post-traumatic stress disorder—all associated with chronic pain—have all been associated with the COVID-19 pandemic. Anxiety and increased awareness around physical symptoms have become common during the pandemic; patients with increased physical awareness are more likely to experience chronic pain.

In addition to these physical and psychological influences from the pandemic, social landscapes have been dramatically altered by necessary public health responses to limit viral spread. Face-to-face health care services, including pain management, have been restricted. Many people have experienced a change in employment status, influencing both social activities and stress. Homeschooling has forced parents to alter their daily roles and routines. Weak social ties, important for a sense of community, have been eliminated because fewer incidental positive interactions, such as those with a regular barista, occur during social distancing enforcement. Social trust has been decreased in part by necessary risk management to avoid SARS-CoV-2 infection, which intensifies existing social tensions because people use existing prejudices to guide decisions surrounding whom to trust. Hostile or abusive relationships worsen pain, and domestic abuse rates increased during the pandemic. Psychological disturbances, reduction of medical services, stress, loss of a sense of community, and experiencing abuse can all intensify existing, or increase risk for developing, chronic pain. Less social contact can cause feelings of loneliness, which are associated with increased pain intensity and new pain development of pain. Post-COVID, the epidemiology of chronic pain is likely to change.

Despite all of these changes known to exacerbate pain, some opportunities have emerged for chronic pain sufferers. For some patient populations, telemedicine and digital interventions for pain management increase access to care and have comparable outcomes to in-person care. The widespread implementation of telehealth reduced waitlists and cancellations. Chronic pain patients have reported that lower burdens of social participation have improved their ability to manage their pain, whereas social ties with one’s household members have been strengthened by pandemic conditions. Such strong relationships, when healthy, reduce loneliness and pain.

The magnitude of both benefits and risks are influenced by demographics. High dropout rates are observed with technology-based interventions in age-, disability-, socioeconomic status-, and first-language-dependent ways. The most socioeconomically disadvantaged groups are most likely to be adversely affected by the COVID-19 pandemic, physically, psychologically, and socially, and are therefore the most vulnerable to increased pain. Reduced access to telehealth and nonpharmacologic treatments such as acupuncture and physical therapy have increased use of pharmacologic analgesic strategies, with the associated risks of side effects and addiction. Addressing these risks requires that health care providers acknowledge and are responsive to patients’ social contexts when assessing pain during the pandemic.

Mindfulness-Oriented Recovery Enhancement Treats Comorbid Chronic Pain, Opioid Misuse, and Psychiatric Disorders by Targeting Hedonic Dysregulation

Eric Garland, PhD, LCSW; University of Utah

The term “disease of despair” in sociological and epidemiological literature, when used to describe the opioid crisis, not only is a metaphor, but also describes the pathogenic mechanisms that create and facilitate opioid use disorder as well as those that link chronic pain to opioid misuse. Dr. Garland emphasized the need to understand the role of hedonic dysregulation in pain, pleasure, and addiction. Modern neurobiology suggests that pleasure and pain are not opposites, but rather share a common pathway involving the mesocorticolimbic dopamine circuit and the endogenous opioid system. Most patients prescribed opioids for chronic pain do not misuse or become addicted to them. Dr. Garland has structured his basic science research program around determining why some patients become addicted whereas others do not.

Using an experimental paradigm that assesses selective attention, Dr. Garland's team determined that chronic pain patients addicted to opioids display attentional bias toward opioid cues. Opioid-addicted chronic pain patients could not self-regulate their autonomic reactions to opioid cues, suggesting that opioid misuse is associated with hedonic dysregulation. Relative to chronic pain patients who take opioids as prescribed, those who misuse opioids have deficits in the capacity both to down-regulate negative emotional reactions with reappraisal (i.e., the cognitive process of re-framing the meaning of a stressful life event) and to up-regulate positive emotional responses by savoring natural healthy rewards.

Dr. Garland developed Mindfulness-Oriented Recovery Enhancement (MORE), an integrative mind-body therapy that unites complementary aspects of mindfulness training, third wave cognitive behavioral therapy (CBT), and positive psychology into a treatment that can simultaneously target addictive behavior, emotional distress, and chronic pain. This therapy begins with the foundation of mindfulness training which, by virtue of its effects on increasing attentional control and meta-cognitive awareness, is thought to synergize more elaborate therapeutic techniques such as reappraisal and savoring. In MORE, patients are taught a mindful savoring technique, practicing by focusing mindful attention on a rose, appreciating multisensory inputs from that rose. This technique is intended to amplify natural reward processing in the brain, induce positive affect analgesia, foster experiences of meaning, and elicit self-transcendence (i.e., the sense of being connected with something greater than the self). Through the integration of mindfulness, reappraisal, and savoring practices, MORE modifies associative learning mechanisms dysregulated during the allostatic process of addiction by strengthening top-down cognitive control and restructuring bottom-up reward learning from valuing drug rewards to valuing natural rewards.

Dr. Garland’s team found that, compared to an 8-week supportive psychotherapy control condition, 8 weeks of MORE significantly reduced opioid misuse and chronic pain severity, while increasing mindfulness, reappraisal, and savoring. EEG data suggested that patients who participated in the MORE program had decreased drug-cue-reactivity and increased positive emotional reactions to naturally rewarding images. Nine months after the treatment program, MORE patients reported a 46 percent reduction in opioid misuse as compared to 22 percent reduction in the active control group, and 36 percent of patients in MORE reduced their opioid dose by half or greater.  Notably, the patients had not been expressly encouraged to reduce their dose and did so of their own volition. MORE improved an array of dimensions of psychological health, including depression symptoms, PTSD, positive emotions, sense of meaning in life, and self-transcendence. MORE significantly increased reported pleasant sensations in the body and shifted the ratio of pleasant to unpleasant sensations. These data suggest that increasing sensitization to natural pleasure, joy, meaning, and transcendence may eventually outweigh the pull of drug-related reward and thereby reduce addictive behavior. MORE’s success has continued during the COVID-19 pandemic, when the treatment program shifted from in-person to remote using Zoom, with the addition of interventions such as smartwatches that detect physiological indices of stress and prompt the patient to practice their skills.

Sleep Disruption, Pain, Inflammation and Positive Affect: Effect of Comorbidities on Pain with Reference to the 2020 COVID-19 Pandemic

Michael T. Smith, PhD; Johns Hopkins University

Dr. Smith discussed how sleep and pain are related and how the COVID-19 pandemic has affected both. He provided a conceptual overview of how inflammation may be a shared common mechanism explaining high comorbidity rates with insomnia, depression, and pain. Notably, during the pandemic, rates of insomnia, depression, and related mental health symptoms have multiplied by two to three times among the general population. Sleep loss decreases positive affect more than it increases negative affect. Sleep disturbances have become 50 percent more common. Notably, increases in pain, insomnia, and depression have affected Black Americans more than other populations. 

Sleep disruptions also disrupt the immune system; among people with droplets of rhinovirus placed intranasally, those who slept fewer than 5 hours per night had four times the risk of contracting a cold than those who slept 7 hours. Cytokines, a key class of immune proteins, cause fever, inflammation, pain, and feelings of malaise. Heightened inflammation, in particular, is seen in most pain disorders, sleep conditions, and depression.

One extreme insomnia phenotype is the objective short sleeper phenotype, defined as sleeping less than 6.5 hours per night alongside other insomnia symptoms. The phenotype is correlated with heightened systemic inflammation, especially in adolescents, and is particularly common in Black women. In one study, Black insomniacs had only an 11 percent chance of having normal sleep duration, whereas white insomniacs had a 78 percent chance. The objective short sleeper phenotype is correlated with higher pain severity, higher rates of psychological symptoms, pain catastrophizing, functional jaw limitations, greater cytokine concentration, heightened pain sensitivity, hypertension, and heightened measures of central sensitization. To test causality, Dr. Smith’s team subjected patients to a forced awakening experiment during which they experienced only 4 hours of noncontinuous sleep in a night. Patients exhibited hyperalgesia and an increase in cellular inflammation.

Dr. Smith emphasized that the COVID-19 pandemic has increased insomnia, depression, and chronic pain severity in a race- and gender-dependent manner. He further noted that the expansion of telehealth associated with the pandemic may have exacerbated existing health disparities, although evidence is currently lacking.

Panel Session Q&A

Savoring

Dr. Garland noted that no patients have reported using the savoring skill to savor opioids they are abusing. He also noted that as part of the MORE program, patients are encouraged to practice mindfulness before using an opioid and to consider whether they are doing so for pain relief or another reason, such as to relieve cravings or negative affect. Patients have reported magnification of analgesic effects if they practice mindfulness before using an opioid, which Dr. Garland suggests may indicate that mindfulness operates through an opioidergic mechanism.

Dr. Garland stated that savoring is multidimensional and can be employed not only for purely sensory experiences, but also for social interactions and memories of loved ones. The savoring skill ranges from the hedonic level to the eudaimonic level.

Social Factors and MORE

Dr. Garland noted that social factors influence group therapy, but that he does not know how they might influence MORE, which is twice as effective as group therapy. Dr. Ashton-James noted that in Australia, people in remote and rural communities are often reluctant to engage with psychological therapies, including mindfulness and CBT, suggesting a social and potentially cultural barrier.

Empathy in Telemedicine Settings

Dr. Ashton-James noted that all research regarding patient-provider communication has occurred in face-to-face settings, and that studies regarding empathic techniques in remote or telehealth settings would be valuable. Dr. Ashton-James added that tailoring telehealth experiences to patient preferences may aid their therapeutic experience; for example, the use of virtual reality can modify how physicians respond to their patients and how they present themselves.

Social Factors and MORE

Dr. Garland noted that social factors influence group therapy, but that he does not know how they might influence MORE, which is twice as effective as group therapy. Dr. Ashton-James noted that in Australia, people in remote and rural communities are often reluctant to engage with psychological therapies, including mindfulness and CBT, suggesting a social and potentially cultural barrier.

Timing of Sleep Disruptions

Dr. Smith stated that although he cannot answer with certainty whether the specific time of awakenings impacts pain or inflammation, sleep is cyclic. He hypothesized that because deep sleep occurs mostly in the first third of the sleeping period, depriving a person of slow-wave sleep by awakening them during this time may amplify pain experience, whereas awakening a person later in their sleeping period may disrupt random eye moment sleep, which may impact emotional regulation more. People with delayed circadian sleep phases tend to have more pain, more depressed mood, and greater addiction potential.

Keynote Address: Neural Mechanisms of Prosocial Behavior

Robert C. Malenka, MD, PhD; Stanford University

Dr. Malenka presented on the neural mechanisms of pro-social behavior. Through a series of studies using mouse models of autism and 3, 4-Methylenedioxymethamphetamine (MDMA), Dr. Malenka concluded that serotonergic projections from the dorsal raphe to the nucleus accumbens (NAc) drive pro-social behavior. These prosocial behaviors contribute to the behavioral antecedents of empathy in mice; mice tend to spend more time around other mice in pain than pain-free mice. Dr. Malenka suggested that these prosocial mechanisms may also explain the social transfer of pain; after exposure to another mouse in pain (e.g., intraplantar Complete Freund’s Adjuvant [CFA] injection), a previously pain-free mouse will exhibit pain behaviors such as allodynia and hyperalgesia. The mouse that acquired its pain through observation and social transfer does not localize the pain in the same way as the mouse with directly induced pain—the CFA-injected mouse shows allodynia only in the injected foot, whereas the bystander mouse shows allodynia in both feet, suggesting a central mediation of this social acquisition of pain. Both mice show decreased tolerance for the heat pain of tail immersion in aversively hot water. That pain expression also works to influence new observing mice in the same way; the bystander mouse who acquired pain socially influences pain-free mice to spend more time with it.

Dr. Malenka asked whether social transfer of pain was associated with the same neural mechanisms as the prosocial behavior induction of MDMA. Studies using optogenetic manipulation suggested that this empathic pain behavior is mediated by anterior cingulate cortex projections into the NAc and can be both weakened and strengthened by strengthening or inhibiting those projections. Dr. Malenka then hypothesized that if social transfer of pain is mediated by this circuit, social transfer of analgesia may also be controlled by this circuit; those mechanistic experiments have yet to be conducted.

Q&A

Dr. Malenka’s lab is currently testing whether MDMA promotes the social transfer of analgesia or pain and plans to test whether a serotonin-1B agonist, known to facilitate pro-social behaviors, could serve as a therapeutic for chronic pain patients. Dr. Malenka suggested studying whether the same hypothesis regarding NAc serotonin applies to COVID-19 patients and people suffering from COVID-19-related sociability deficits.

Mitchell Max Awardee Introduction

Rena D’Souza, DDS, MS, PhD; Director, NIDCR

The NIH Pain Consortium Mitchell Max Award for Research Excellence honors Dr. Mitchell Max for his lifetime contributions to pain research. The award has been presented annually to an outstanding junior investigator since 2009. Criteria for selecting finalists include the quality of poster abstracts, relevance of the work to advancing pain research, and significance of the scientific question addressed. 

The 2021 Mitchell Max Award finalists included Dr. Melissa Accordino, who studies breast cancer care delivery, survivorship, and care disparities; Dr. Jo Armour Smith, who studies movement control of the trunk and how impairments in the multisensory processes underlying trunk control contribute to pain and movement dysfunctions; and Ms. Daisy Cantu, who received the Mitchell Max Award for her work assessing neuroanatomical mechanisms underlying sex differences in the stress exacerbation of chronic orofacial pain. 

Mitchell Max Awardee Presentation

Stress Exacerbates Orofacial Pain Behaviors to a Greater Degree in Female Rats

Daisy J. Cantu; Texas Women’s University, Denton, TX

Many idiopathic chronic pain disorders, including fibromyalgia, temporomandibular disorder, and osteoarthritis, are more prevalent among women than men, and women are two times as likely to experience stress-related mental illnesses. Despite this gender imbalance, most preclinical studies investigating the role of stress on orofacial pain have been conducted using only male rats.

Trigeminal ganglia signal directly to the brain via cranial nerves 1, 2, and 3, which project to the trigeminal nucleus caudalis (TNC) and parabrachial nucleus (PBN), a region that responds to pain and stress. As compared to stress-free periods, fewer astrocytes are observed in the prefrontal cortex during chronic stress; during orofacial pain, more astrocytes appear in the TNC and PBN than are seen during pain-free periods. Recent transcriptomic studies indicated that astrocytes may be neuroprotective during stress, contradicting earlier beliefs that they were pathologically central to many stress-related illnesses.

Ms. Cantu hypothesized that sub-chronic stress evokes greater orofacial pain behaviors and glial activity in the ascending trigeminal pain pathway in female rats than in male rats. To test this hypothesis, she injected CFA into male and female rats’ vibrissal pads and measured the development of mechanical allodynia. Baseline mechanical sensitivity did not vary by sex, but post-CFA allodynia was greater in females. She used the forced swim stress test as a model of sub-chronic stress, during which male and female rats exhibited comparable levels of stress. However, while allodynia in males did not increase post-swim, it did in female rats, suggesting that stress exacerbates orofacial pain to a greater degree in female rats and supporting the first part of her hypothesis. Ms. Cantu observed an increase in PBN astrocytes in stressed males compared to a sham condition, but a reduction in PBN astrocytes in stressed females compared to a sham condition. Ms. Cantu plans to measure glial fibrillary acidic protein in the PBN and trigeminal nucleus caudalis, measure blood corticosterone levels, and analyze neurochemistry during the stress-exacerbated orofacial pain state.

Q&A

Ms. Cantu plans to repeat this experiment with other pain models, including inflaming the temporomandibular joint to study the distribution across sexes of temporomandibular disorder. She is not aware of any sex differences in infiltrating immune cells in the PBN and trigeminal nucleus caudalis in response to orofacial inflammation and noted that her hypothesis regarding sex differences in astrocytic proliferation in these regions influencing sex differences in pain and stress response is novel.

Junior Investigators Session

Moderator: Leah Pogorzala, PhD; NINDS

Throughout the meeting, junior investigators presented on a wide array of topics. These topics included stem-cell induced antinociception, pain control in the context of Alzheimer’s disease and related dementias, the role of the kappa opioid receptor in pain, and pain trajectories in breast cancer patients of racial and ethnic minorities. The full list of presenters in alphabetical order is available in Appendix C, and presentation abstracts are viewable on the NIH Pain Consortium website.

Panel Session: Interventions for Reducing Pain Health Disparities

Moderator: Cheryse A. Sankar, PhD; NINDS and Yolanda Vallejo, PhD; NCATS

Perspective on Living with Chronic Pain

Norma Guzman

Ms. Guzman shared her experience living with chronic pain caused by a severe car accident and described how her cultural background shaped her response to the pain. After the accident, Ms. Guzman acquired memory, eyesight, sleep, dizziness, and concentration problems. She experienced anxiety attacks and found it challenging to complete simple tasks such as dressing, reading, or watching television. She found that her entire body was in pain, and that chewing would lead to half her face feeling numb, inhibiting her speech. She felt like a spectator rather than a participant or member of her family. She did not work for 5 years.

A second car accident led to a PTSD-like flashback, during which she relived her first accident; afterwards, she experienced symptoms that had resolved years earlier. At times, she could not bend her knees or feel her legs. She finally asked her doctor for help. At times, she could not bend her knees or feel her legs.

Recently, Ms. Guzman started to visit a chiropractor and therapist, as well as her primary care physician, and her symptoms have improved. Although she experiences pain at all times, her life is improving each day and she can now enjoy activities and complete tasks that were impossible for her in the aftermath of the accidents. Ms. Guzman also stated that her religious faith provided solace and support during her recovery.

Addressing Racial/Ethnic Disparities in the Management of Chronic Diseases and Multimorbidity

Ana Quiñones, PhD; Oregon Health & Science University

Dr. Quiñones discussed her team’s efforts to address racial and ethnic disparities in health management of vulnerable older adults with multiple chronic conditions. Dr. Quiñones outlined the generations of health equity research. The first generation documented the existence of health inequities; the second explained the reasons for the inequities and explored mechanisms that underlie and perpetuate them; the third developed interventions to reduce and eliminate these inequities.

Multimorbidity—having two or more concurrent chronic diseases—have compounding effects on health outcomes, leading to effects greater than the risks attributable to any individual chronic disease. Multimorbidity is highly prevalent and disabling, particularly in older people, and is costly to health care systems. Pain in particular is a symptom that dramatically impacts health-related quality of life. Multimorbidity accumulates differently by race and ethnicity; middle-aged African Americans have a higher level of chronic disease burden than age-matched whites and Latinx individuals. They develop additional chronic conditions on average 4 years earlier than their white counterparts. Latinx individuals have a comparable initial level of chronic disease but develop additional chronic diseases at a faster rate than whites.

Using Latent Class Analysis, a statistical strategy that involves dividing a group into classes based on similar categorial or continuous variables, Dr. Quiñones’s team identified multimorbidity combinations, including both physical and mental health conditions. Black and Latinx study participants were more likely than white participants to be in the class defined by complex multisystem comorbidities after 16 years and were more likely to die or be lost to follow-up compared to their white peers, even after accounting for initial class membership.

This work described existing health inequities; the next step for Dr. Quiñones’s team is to determine how best to support vulnerable older adults with complex care needs. To achieve this goal, the team must hear directly from patients, considering not only co-occurring diseases but also personal situations, which contextualize morbidity burden and the resources available to patients to manage that burden. To develop interventions, adaptation and implementation science will inform understanding of which interventions work under which circumstances and for which patients. Finally, health care delivery models must continue to innovate to shift focus from centering acute care needs to centering chronic care needs, not only for persons seen in the clinic but also for community services and programs.

Social Determinants of Health in American Indian Populations

Donald Warne, MD, MPH; University of North Dakota

Dr. Warne presented on the current and future social determinants of health in American Indian and Alaskan Native (AI/AN) populations. Because AI/AN populations are both small and relatively concentrated (only seven U.S. states have a population that is at least 3 percent AI/AN), they are often not included in national datasets. That lack of inclusion limits the ability to track and understand issues pertaining to these populations, including multimorbidity and pain syndromes.

Much as with African Americans, historical maltreatment has shaped AI/AN populations and historical trauma has driven chronic stress and chronic pain. Colonization is the primary reason for the concentration of AI/AN populations. An often-ignored form of historical trauma was forced boarding school participation, during which much abuse and neglect occurred. Dr. Warne noted that his mother was a boarding school survivor, emphasizing that this history is not far distant. Gestational stressors impact fetal development and the future health of the child; due to high rates of unplanned pregnancies and young people experiencing trauma and addiction, gestational stressors are widespread in AI/AN populations. The South Dakota Health Survey indicated that American Indians in the state had significantly higher Adverse Childhood Experience (ACE) scores than the general population, which led to post-traumatic stress and long-term challenges with both mental health and physical health. Strong correlations exist between ACEs and higher rates of diabetes, heart disease, cancer, and pain syndromes. Recently, CDC’s National Center for Injury Prevention and Control revamped its pyramid representing how ACEs lead to early death, adding “historical trauma and generational embodiment” leading to “social conditions and local context” before ACEs. ACEs disrupt neurodevelopment; impair social, emotional, and cognitive development; encourage adoption of risky health behaviors; and lead to early onset of disease, disability, and death.

AI/AN adults also experience stress, caused by poverty, unstable communities, racism, and discrimination. People with pain syndromes living in stressful conditions generally have worse pain outcomes than those in non-stressful conditions; looking upstream and addressing earlier factors involved in the pain syndrome can reduce the impact of these conditions. Addressing social determinants of health and sources of toxic stress can dramatically improve living conditions for a population and reduce self-medication behavior.

In hopes that including AI/AN clinicians and researchers in the medical and scientific fields will accelerate identification of solutions to these issues, Dr. Warne is Director of the “Indians into Medicine” or “INMED” program at the University of North Dakota, through which more than 250 American Indian physicians have graduated since 1973. He has also developed an Indigenous Health specialization at the MPH level and a new Indigenous Health PhD program, through which the next generation of indigenous health researchers can be trained not only in research methods, but also in recognition of historical and cultural traumas, as well as cultural means of addressing health disparities, such as increasing connectivity to culture, language, and ceremony.

GOALS Program Design: Adapting Evidence-Based Interventions for Medically Underserved Populations with Chronic Pain

Katrina Maluf, PT, PhD; San Diego State University

Dr. Maluf noted that interventions developed specifically for minority communities are uncommon. To illustrate this rarity, she described how a PubMed search for systematic reviews of chronic spinal pain interventions revealed 300 articles over 20 years but adding minority health to the search reduced that number to zero. Primary studies of chronic pain interventions adapted for the specific purpose of improving minority health outcomes number only 19 over the same 20-year period. Drs. Maluf and Gombatto developed the Goal Oriented Activity for Latinos with Spine Pain (GOALS) study, which aims to systematically adapt an existing physical therapy intervention to improve health outcomes for Latinx people with chronic spine pain. To effectively and systematically adapt existing evidence-based interventions for marginalized communities, researchers must incorporate the opinions of those communities from the outset.

Dr. Maluf’s team chose to use intervention mapping (IM), specifically the IM-Adapt framework, to guide the adaptation process, which begins with a needs assessment, is followed by development of an intervention logic model (graphical depiction of processes communicating underlying assumptions and specific intended results), and ends with selection of an existing intervention. The adaptations target five major domains (intervention delivery, content, activities, materials, and design). When Dr. Maluf and her team reviewed electronic health records, they found low rates of follow up for physical therapy referrals for chronic spine pain across all races and ethnicities that were lowest among Latinx patients, only 30 percent of whom attended physical therapy when referred by their primary care physician. The most commonly cited reasons for non-adherence were scheduling and transportation issues along with the belief that physical therapy would not help resolve symptoms.

Dr. Maluf’s team chose to adapt the Changing Behavior through Physical Therapy (CBPT) telehealth program, a process that took place over a 2-year period followed by consensus panels that evaluated, modified, and validated culturally relevant outcome measures. The team regularly consults with community partners and an adaptation advisory panel that includes members of the Latinx community and content experts in physical and psychological rehabilitation, cultural adaptation, and dissemination methods. The team conducted provider training sessions and pilot studies of both the original CBPT and adapted GOALS interventions, followed by semi-structured patient interviews with rapid qualitative analysis of patient perspectives. A notable challenge to implementing GOALS was an initial reluctance by Federally Qualified Health Centers and associated providers to consider telehealth interventions due to safety concerns, as well as lack of infrastructure and reimbursement mechanisms for remote visits. This reluctance changed rapidly with the onset of the COVID-19 pandemic.

The GOALS intervention logic model guided decision-making in this process and determined that the “active ingredients” that must be preserved during adaptation include functional movement training, cognitive-behavioral skill training, graded aerobic activity, and impairment-based therapeutic exercise, each coupled with motivational interviewing to facilitate goal setting. Ultimately, these elements are expected to optimize treatment outcomes for the target population. The team adapted materials to become more culturally relevant and broadly accessible (e.g., professional illustrations and translation into both English and Spanish, adding strategies for communicating needs, and addressing the importance of family interactions within Latinx communities). Pilot studies suggested clinically meaningful reductions in pain intensity and interference for individuals participating in the GOALS program. A full-scale randomized controlled trial will begin enrolling patients in July 2021.

Cognitive Behavioral Pain Management Research: Increasing Access and Dissemination to Reduce Pain Disparities

Lisa Campbell, PhD; East Carolina University

Dr. Campbell noted that pain treatment is inadequate for most people, and especially so for marginalized populations. When medication prescription is reduced to limit spread of opioid addiction, access to pain management decreases unless access to non-pharmacological treatments increases. Often, pain disparity researchers and treatment development researchers do not communicate, limiting the ability to reduce disparities in clinical care and research. Logistical and financial barriers have historically received the most attention. Secondary access barriers, however, including stigma, literacy, and cultural considerations, require more nuance to address. Oftentimes, behavioral care providers resist interventions that are designed to address disparities as well as pain because they necessarily change existing practices. Many community care clinics focus on medical disease management imperatives, which often conflict with the more behaviorally directed interventions developed to combat health inequities.

To change this dynamic, Dr. Campbell’s team attempted to bring the research center to the marginalized populations rather than bring the marginalized populations to the research center. The team built a psychosocial interventional study called Project Lazarus within the local clinic setting, earning buy-in from clinical leadership by emphasizing the underlying research. The project compared pain education to CBT-based pain management targeting pain, function, and depression. The project integrated cultural considerations and was based in two large college towns in low-resource regions  with similar population demographics, economic conditions, high disability levels, and high opioid crisis impacts (i.e., Tuscaloosa, Alabama, and Greenville, North Carolina). Lack of internet access and digital tools were of particular concern for dissemination. In the past year, the group has focused on using the Learning About My Pain (LAMP) study, and it expects that offering a choice of delivery medium including hybrid options incorporating both in-person and virtual health care will benefit patients by offering them choices post-pandemic.

How Understanding Pain Biology Could Facilitate Targeted Analgesics to Reduce Pain Management Disparities in Individuals Living with Sickle Cell Disease

Amanda Brandow, DO, MS; Medical College of Wisconsin

Dr. Brandow studies the drivers of the heterogeneity of pain and pain trajectory in sickle cell disease patients, as well as ways to leverage knowledge of the underlying pain biology to design targeted therapeutics with greater analgesic efficacy. Sickle cell disease is the most common inherited blood disorder in the United States and is caused by a mutation in hemoglobin leading to sickle-shaped red blood cells, vaso-occlusion, and tissue ischemia that affects 1 in every 400 African Americans. Very severe acute and chronic pain are the most common complications of sickle cell disease, and likely result from vaso-occlusion and tissue ischemia. In infancy, toddlerhood, and early childhood, patients with sickle cell disease often experience intermittent severe acute painful episodes leading to hospitalization and intravenous opioid therapy. In adolescence and adulthood, most patients experience refractory chronic daily pain in addition to severe acute intermittent pain episodes or “pain crises.”

However, sickle cell pain severity is very heterogenous, with 40 percent of patients reporting severe, 35 percent intermediate, and 18 percent mild pain. This heterogeneity contributes to disparities in pain management, as does the inability to predict phenotypic pain expression in infants diagnosed with the same condition. Patients often face difficulty accessing comprehensive pain care due to a combination of stigma, negative provider attitudes, and racial bias, the experience of which increases suffering from pain and negatively impacts pain care delivery. The pain biology of sickle cell disease is poorly understood, and few studies address this refractory pain condition, further contributing to negative provider attitudes.

Nociceptive pain is likely driven by chronic inflammation and ischemia-caused tissue damage, and neuropathic pain is associated with both central sensitization and psychosocial factors such as depression, anxiety, sleep disorders, and social determinants of health. Dr. Brandow argued for understanding sickle cell disease as a chronic inflammatory disorder. Cytokines and chemokines are elevated at baseline for patients with sickle cell disease, and both proteins increase further during episodes of severe acute pain. Robust transcriptional signatures, indicating significant innate immune components, distinguish the peripheral blood mononuclear cells of patients with sickle cell disease from those of matched healthy controls. Dr. Brandow’s team is further investigating these pathways and aims to correlate them with phenotypic pain data. She hopes to delineate novel pathways for targeted analgesic treatment and to develop an immune-based prognostic biomarker for sickle cell pain.

Roundtable Discussion on Intervention to Reduce Pain Health Disparities

Limitations of Research Populations

Dr. Quiñones noted that existing research tends to focus on single conditions, when in reality patients are more likely to have multiple conditions (multimorbidity). Representing this medical complexity in research would be valuable, because models of multimorbidity and health disparities aid researchers in developing interventions that account for each patient’s total circumstance, instead of addressing specific conditions in isolation. Dr. Warne agreed and expanded on her earlier comment that research does not represent real patient populations—evidence-based medicine is often tested in homogenous populations, rather than those most in need of treatment. Similarly, AI/AN health would benefit from increased numbers of American Indian investigators who can more easily earn trust from those populations, and because lived experience means that an American Indian investigator would more likely know what affects those populations.

Choosing Interventions for Adaptation

Dr. Campbell stated that adapting interventions to fit the cultures of minoritized communities and building an evidence-base from which to develop new interventions are critical steps to reducing health care disparities over the long term. Dr. Maluf agreed, stating that, to determine whether one strategy to reduce disparities is better than another, researchers must first conduct a needs assessment for a specific population and partner with community representatives. Dr. Warne noted that traditional study designs are often inadequate for studying culturally relevant treatments because many such treatments involve religious ceremonies and practicing a form of mindfulness about healing, preventing double-blind and placebo-controlled trials. Dr. Sankar noted that developing studies to address such treatments requires familiarity with the culture and therefore echoed Dr. Warne’s comment about a need for more  researchers from minority populations.

Historical Trauma

Dr. Warne stated that the first step to structurally intervening to interrupt or begin to heal historical trauma is to acknowledge its existence. In addition, the scientific community should embrace the use of culturally based interventions that already exist to address trauma. Stress worsens many health conditions and focusing on relieving that stress is critical to reducing health disparities.

Impact of Sickle Cell Disease on Patients’ Whole Lives

Dr. Brandow stated that sickle cell disease often causes strokes that can induce neurocognitive abnormalities, which introduce complexities into settings where pain management can already be challenging. Most people living with sickle cell disease in the United States are Black and impoverished. This disease shapes not only individual lives, but also the lives of entire families, and even curative therapies such as stem cell transplant often do not relieve pain.

Impact of Language

Dr. Maluf stated that her team considers the effects of language and literacy on program efficacy by hiring bilingual therapists who deliver the same intervention in either English or Spanish, or at times, “Spanglish,” a mix of the two, depending on patient preference.

Cultural Humility

Dr. Campbell noted that a working group focused on anti-racism in pain research integrates the concept of cultural humility. As an extension of this concept, she emphasized digital disparities, which many researchers do not consider because their lived experience does not involve underserved rural areas with limited internet access. Dr. Maluf agreed but emphasized that institutional barriers such as limited provider time and digital and internet infrastructure pose challenges. Developing interventions that fit into existing health care systems, training providers, and installing necessary technology is central to successful trials involving clinics in the field. Dr. Campbell noted that intervention research should be framed within the system for first design.

Benefits of Provider Relationships

Ms. Guzman believes that her doctors were extremely helpful and that her pain experience was worse than it might have otherwise been largely because of cultural beliefs that reinforced an inability to ask for help or admit to suffering, as well as her previous lack of health literacy. In addition, the doctors who most helped her were patient and made her feel listened to. Dr. Maluf echoed that many patients she has treated or included in studies stated that one-on-one attention with physical therapists was most effective and helpful, even for conversations over the phone rather than direct in-person contact and evaluation, which often hamper conversations when done in busy or crowded clinics.

Closing Remarks

David Shurtleff, PhD; Deputy Directory, NCCIH

Dr. Shurtleff closed the meeting by emphasizing that the COVID-19 pandemic has exposed the existing health disparities and structural racism that have persisted for centuries. Vulnerable groups include those of lower socioeconomic status, racial and ethnic minorities, older adults, women, children, active service members, and cognitively disabled people. The current structure of the health care system disadvantages these groups further. He reiterated Dr. Fritz’s early comment that, currently, the United States finds itself combatting many epidemics, including COVID-19, opioid misuse, pain management, and systemic and structural racism. These epidemics have compounded each other, increasing suffering for many. Dr. Shurtleff thanked the two speakers who provided their perspectives as patients and noted that the issues discussed during the Symposium will persist in coming years, as patients like Lt. Banas seek health care to address the lingering symptoms of their COVID-19 infections. 

In response to the COVID pandemic, the rate of technological development accelerated to accommodate a need for telehealth practices. Innovations in technology and use of smart devices can either exacerbate or ameliorate disparities. Researchers and clinicians must confront the risks of perpetuating or exacerbating existing inequalities and develop strategies to avoid causing additional harm.

Finally, Dr. Shurtleff reiterated the need for cultural humility when approaching social groups different from one’s own and how that mindset should influence actions such as study design. Addressing patients holistically and compassionately typically leads to better outcomes, which extends beyond the individual to their community. Dr. Shurtleff ended his remarks with the activist phrase, “Nothing about us without us is for us.”