Treating Chronic Pain in Sickle Cell Disease — The Need for a Biopsychosocial Model
Chronic pain is the most common complication affecting adults with sickle cell disease (SCD).1 Pain profoundly affects people’s quality of life, functional ability, and health care utilization. Clinicians are often unsuccessful at addressing chronic pain in SCD, especially among the large number of patients for whom nonopioid analgesics aren’t sufficient and those who have developed opioid tolerance. Why aren’t we doing better?
We believe the medical community is looking at sickle cell pain through the wrong lens — treating it as a hematologic problem, while overlooking the neurologic, psychological, and social aspects of chronic pain. Given the current understanding of the neuropsychology of pain, the health care system has the ability to manage sickle cell pain more effectively. Doing so will require accepting a broader understanding of the experience of pain and devoting adequate resources to addressing its multiple dimensions.
The biopsychosocial model helps capture people’s experience of chronic pain by affirming that biologic, neuropsychological, and socioenvironmental elements play a role in pain-related processes. Biologically, acute vaso-occlusive events in SCD cause tissue inflammation and nociceptive pain. This concept remains the primary model used in clinical practice to understand sickle cell pain and justify analgesic therapy.
Many adults with SCD, however, have chronic daily pain without indicators of vaso-occlusive pain. Adults with a chronic-pain phenotype have nerve damage, chronic inflammation, and sometimes central sensitization. They frequently have allodynia and hyperalgesia. Even patients who have received successful curative therapies, such as a bone marrow transplant or gene therapy, may continue to have chronic pain. These findings suggest that chronic pain in adults with SCD is complex and that a model based principally on hematologic processes is inadequate for understanding and managing it.
Chronic pain that is affected by neuropsychological factors is common to many disease processes, and the medical field’s understanding of the basis for this type of pain has advanced over the past decade. Prolonged or repeated episodes of nociceptive pain result in neural changes that enhance pain sensitivity, heighten pain anticipation and aversion, and cause synaptic networks involved in emotion and cognition to prioritize painful stimuli over pleasurable ones. In addition, emotional trauma associated with pain experienced on a single occasion can enhance negative emotions during future episodes. All these factors contribute to a subjective experience of pain as prolonged, persistent, overwhelming, and urgent, even in the absence of nociceptive stimuli.
How is this experience reflected in common health care scenarios? One hypothetical example involves an adult with SCD who is being treated with long-term opioid therapy and comes to an emergency department with severe pain. If she appears to be in distress and her diagnostic tests suggest acute vaso-occlusive pain, she will probably be admitted for treatment and receive analgesics adjusted to a dose to relieve her pain. If she doesn’t display the expected signs of distress, and if her lab work doesn’t support a diagnosis of a vaso-occlusive event, however, there is a good chance that she will be labeled as “drug seeking.” This label, which delegitimizes the patient’s account of her pain, is powerful. Once she is labeled a “drug seeker,” the patient may be sent home without treatment at the physician’s discretion.
This scenario illustrates why relying on the hematologic model of sickle cell pain provides insufficient guidance for clinical decision making. Is the patient exaggerating or falsifying pain if there is no apparent nociceptive stimulus? Does the patient “deserve” aggressive pain treatment? Will opioid treatment help the patient, or will it potentiate a harmful dependence? The hematologic model doesn’t encompass factors affecting pain that derive from experiences with various forms of structural violence, including historical inequity, trauma, and racism. These factors affect not just the life circumstances of adults with SCD, but the neuroanatomy and synaptic processing that underlie their experience of pain.
Historically, adults with SCD, the majority of whom are people of color, have been undertreated for chronic pain. Well into the 20th century, the medical profession maintained, without basis, that people of color are less sensitive to pain than White people. In today’s vernacular, labels such as “drug seeker” and “overutilizer” serve to minimize sickle cell pain and dismiss the patient’s reported subjective experience.
In semistructured interviews conducted by one of our teams, adults with SCD reported profound distress associated with what should have been a powerful act of self-care: seeking hospital-based administration of parenteral opioids for pain flares. They further reported that racism and bias against SCD are woven into their clinical encounters. These findings, which align with reports from other researchers,2 point to a fundamental tension. Adults with SCD must seek acute pain relief in a White-dominated health care system. The system may arbitrarily grant or refuse their request for pain relief, a reality that embodies racism in that such encounters are marked by White authority over the bodies of people of color. Such experiences are profoundly traumatizing for patients.
The harmful effects of the health care system dismissing the pain of adults with SCD go beyond an immediate lack of pain relief for patients. Uncertainty about access to treatment forces patients to devote more cognitive resources and, at the behavioral level, more time and effort, to obtaining pain treatment. Neurologically, the repeated failure of pain-relief efforts enhances awareness of, attention to, and distress caused by nociceptive stimuli and produces a prolonged reduction in the threshold for pain perception. Negative or unpredictable experiences seeking pain relief reinforce the neural processes that give rise to chronic pain. In addition, emotions play a powerful role in learning. A single experience that causes emotional trauma can greatly amplify the degree of distress associated with subsequent pain episodes.3
What adults with SCD seek as patients is relief from pain that is often excruciating. Opioids continue to occupy a central place in the treatment of acute and chronic pain in people with SCD, as reflected in the most recent American Society of Hematology pain guidelines. Treatment must be carefully managed to avoid hyperalgesia, tachyphylaxis, treatment failure, addiction, and accidental overdose.
While ensuring that adults with SCD have reliable and unimpeded access to pharmacotherapy, we also need to offer them a broader range of strategies based on medicine’s emerging understanding of the neuropsychological basis of chronic pain.4 Our patients tell us that they want a pain plan that encompasses emotional support, validation, cognitive strategies, and pharmacotherapy. Interventions involving cognitive behavioral techniques, training in mindfulness-based pain management, and multidisciplinary team approaches have reduced pain associated with other chronic conditions. Multilevel interventions that are part of a patient-centered model of pain management could represent a more effective approach to improving quality of life among people with SCD and chronic pain (see box).5
Broadly, the medical community needs to recognize the ways in which patients’ interactions with the health care system create distress and amplify pain and take steps to repair broken care processes. The barriers, delays, and uncertainties that adults with SCD face in obtaining access to pain treatment ultimately intensify their pain and increase the urgency of pain-avoidant behavior, while undermining both patient and institutional goals.
The approaches outlined above will require substantial health care system investment. We believe such investment is justified to improve the quality of care for adults with SCD, who have a lifelong, debilitating disease. If we can help them address the many dimensions of their chronic pain effectively, they may begin to perceive the health care system as a resource in managing their disease, rather than an obstacle to realizing improved health and well-being.
Article Link: https://www.nejm.org/doi/10.1056/NEJMp2301143