Pain is a major comorbidity of sickle cell disease (SCD). Patients with SCD may suffer
from both acute and chronic pain. Acute pain is caused by recurrent and unpredictable
episodes of vaso-occlusive crises (VOC), whereas the exact etiology of chronic pain
is still unknown. Opioids are the mainstay for pain treatment, but the opioid epidemic
has significantly altered access to prescription opioids and has brought concerns
over their long-term use into the forefront, which have negatively impacted the treatment
of sickle pain. Opioids remain potent analgesics but growing opioid-phobia has led
to the realization of an unmet need to develop nonopioid therapies that can provide
relief for severe sickle pain. This realization has contributed to the approval of
3 different drugs by the Food and Drug Administration (FDA) for the treatment of SCD,
particularly to reduce VOC and/or have an impact on the pathobiology of SCD. In this
review, we outline the challenges and need for validation of side-effects of opioids
and provide an update on the development of mechanism-based translational therapies,
specifically targeting pain in SCD.
Abbreviations:
AU (Action Unit), ACS (Acute Chest Syndrome), AAT (Alpha-1-Antitrypsin), ASH (American Society of Hematology), AV (Audio-visual), CaMKII (Ca2+/calmodulin-dependent protein kinase II), CGRP (Calcitonin Gene-Related Peptide), CBD (Cannabidiol), CB1R (Cannabinoid Receptor 1), CB2R (Cannabinoid Receptor 2), CDC (Centers for Disease Control and Prevention), CNS (Central Nervous System), CCL2 (Chemokine c-c motif Ligand 2), COT (Chronic-Opioid Therapy), CoQ10 (Coenzyme Q 10), CBT (Cognitive Behavioral Therapy), COX2 (Cyclooxygenase-2), DA (Dopamine), DRG (Dorsal Root Ganglion), EA (Electroacupuncture), EEG-fMRI (Electroencephalogram-functional MRI), ER (Emergency Room), FDA (Food and Drug Administration), fMRI (Functional Magnetic Resonance Imaging), GFAP (Glial Fibrillary Acidic Protein), HEAL (Helping to End Addiction Long-term Initiative program), HR (Hypoxia-reoxygenation), IL (Interleukin), MOPR (Mu-opioid Receptor), MGS (Mouse Grimace Scale), NHLBI (National Heart, Lung and Blood Institute), NIH (National Institute of Health), NK1R (Neurokinin 1 Receptor), NOPR (Nociceptin Opioid Receptor), N/OFQ (Nociceptin/orphanin FQ), OIC (Opioid Induced Constipation), OR (Opioid Receptor), OIH (Opioid-induced Hyperalgesia), OTC (Over the Counter), PAMORA (Peripherally Acting Mu Opioid Receptor Antagonist), PDGFR-β (Platelet-Derived Growth Factor-β), qEEG (Quantitative Electroencephalogram), QST (Quantitative Sensory Theory), RCT (Randomized Control Trial), ROS (Reactive Oxygen Species), RBC (Red Blood Cells), 5-HT (Serotonin), SNRI (Serotonin-norepinephrine reuptake inhibitor), SCD (Sickle Cell Disease), SP (Substance P), SIRS (Systemic Inflammatory Response Syndrome), THC (∆9-tetrahydrocannabinol), TLR4 (Toll-like Receptor 4), TCD (Transcranial Doppler Ultrasound), TNF-α (Tumor Necrosis Factor-α), TKI (Tyrosine Kinase Inhibitor), VEGFR2 (Vascular Endothelial Growth Factor Receptor 2), VOC (Vaso-occlusive Crisis), VR (Virtual Reality)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: March 09, 2021
Accepted:
March 6,
2021
Received in revised form:
March 2,
2021
Received:
January 4,
2021
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
