Evaluation of non-opioid therapies for pain management of sickle cell disease: a literature-based review

Pain is a debilitating complication of sickle cell disease (SCD), driven by recurrent vaso-occlusive crises and chronic pain syndromes involving central sensitization and neuropathic mechanisms. Although opioid medications remain first-line therapy for acute pain, there are limitations that highlight the need for effective adjunctive approaches. Available data support non-opioid pharmacologic therapies including acetaminophen and nonsteroidal anti-inflammatory drugs as components of multimodal analgesia, with emerging evidence for therapies targeting neuropathic and centralized pain. Non-pharmacologic interventions such as cognitive behavioral therapy have also demonstrated potential benefits as adjunctive strategies in SCD pain management. This literature review examines evidence supporting non-opioid pharmacologic and non-pharmacologic therapies for pain management in SCD and is based on structured searches of PubMed, MEDLINE, and Cochrane databases.