Unmet Need: Mechanistic and Translational Studies of Sickle Cell Disease Pain as a Whole-Person Health Challenge

Sickle cell disease (SCD) is a lifelong monogenic, autosomal-recessive blood disease that predominantly affects individuals of African descent and those who self-identify as Black or Hispanic. Common SCD pathophysiological processes include adhesion, hemolysis, hypoxia, ischemia, oxidative stress, and vaso-occlusion, which often lead to substantial comorbidities and complications. Pain is one of the most common and significant clinical complications for individuals with SCD. Despite advancements in understanding the pathophysiology of SCD, the ways in which SCD pathophysiological processes contribute to nociception and pain signaling, processing, and perception remain largely unclear. Pain management for individuals with SCD is complex and presents unique challenges that must be considered depending on the presenting pain type (eg, acute pain episode vs chronic pain). Racism, stigma (including stigma associated with opioid use), and limited resources present additional challenges. Limited research has been conducted on major clinical features of SCD pain such as its ischemic, inflammatory, and neuropathic components; on its transition from acute to chronic form and across the lifespan; and on factors influencing SCD pain perception. Research on and management of SCD pain requires a whole-person approach, bringing together investigators from multiple disciplines such as hematologists, organ biologists, pain experts, physiologists, neuroscientists, psychologists, geneticists, microbiologists, immunologists, behavioral scientists, and clinicians. Multidisciplinary cross-training, with different platforms for information dissemination and communication, could help promote basic, mechanistic, and translational research to inform the optimization of current treatment strategies and the development of novel therapies for SCD pain. PERSPECTIVE: This review presents the research challenges and negative impact of SCD pain, a grossly understudied condition in a highly underserved population. It also highlights the barriers and opportunities in SCD pain research and could help clinicians better understand current treatment strategies from the whole-person perspective.