Morphine for the treatment of pain in sickle cell disease.
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ABSTRACT:
SUBMITTER: Gupta M
PROVIDER: S-EPMC4306369 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:BackgroundSickle cell disease causes significant morbidity and mortality and affects the economic and healthcare status of many countries. Yet historically, the disease has not had commensurate outlays of funds that have been aimed at research and development of drugs and treatment procedures for other diseases.MethodsThis review examines several treatment modalities and new drugs developed since the late 1990s that have been used to improve outcomes for patients with sickle cell disease.ResultsTargeted therapies based upon the pathophysiologic mechanisms of sickle cell disease that result in organ dysfunction and painful episodes include hydroxyurea, L-glutamine, crizanlizumab, and other drugs that are currently on the market or are on the verge of becoming available. These agents have the potential to improve survival and quality of life for individuals with sickle cell disease. Also discussed is stem cell transplantation that, to date, is the only curative approach for this disease, as well as the current status of gene therapy.ConclusionThese examples demonstrate how the current knowledge of sickle cell disease pathophysiology and treatment approaches intersect. Although interest in sickle cell research has blossomed, many more clinical trials need to be initiated and subjected to more strenuous examination and analysis than have been used in the past.
| S-EPMC6292457 | biostudies-literature
Project description:IntroductionThe contribution of platelet activation to the pathogenesis of sickle cell disease (SCD) remains uncertain. We evaluated the safety and efficacy of eptifibatide, a synthetic peptide inhibitor of the αIIbβ3 receptor, in SCD patients during acute painful episodes.Materials and methodsIn this single site, double-blind, placebo-controlled trial, eligible patients with SCD admitted for acute painful episodes were randomized to receive eptifibatide or placebo at a ratio of 2:1.ResultsThirteen patients (SS - 10, Sβ(0) - 2, SC - 1) were randomized to receive either eptifibatide (N=9; 6 females; median age - 25years) or placebo (N=4; 3 females; median age - 31years). In the intent-to-treat analysis, there were no major bleeding episodes in either the eptifibatide or placebo arms (point estimate of difference: 0.00, 95% CI; -0.604, 0.372). There was one minor bleeding episode in the eptifibatide arm (point estimate of difference for any bleeding: 0.11, 95% CI: -0.502, 0.494). There was no significant difference in the proportion of patients with thrombocytopenia between the treatment groups (point estimate of difference: 0.11, 95% CI: -0.587, 0.495). There were no differences in the median times to discharge, median times to crisis resolution or the median total opioid use.ConclusionsIn this small study, eptifibatide appeared to be safe, but did not improve the times to crisis resolution or hospital discharge. Adequately powered studies are required to evaluate the safety and efficacy of eptifibatide in SCD. Clinicaltrials.gov Identifier: NCT00834899.
| S-EPMC3791139 | biostudies-literature
Project description:Patients with sickle cell disease (SCD) suffer from intense pain that can start during infancy and increase in severity throughout life, leading to hospitalization and poor quality of life. A unique feature of SCD is vaso-occlusive crises (VOCs) characterized by episodic, recurrent, and unpredictable episodes of acute pain. Microvascular obstruction during a VOC leads to impaired oxygen supply to the periphery and ischemia reperfusion injury, inflammation, oxidative stress, and endothelial dysfunction, all of which may perpetuate a noxious microenvironment leading to pain. In addition to episodic acute pain, patients with SCD also report chronic pain. Current treatment of moderate to severe pain in SCD is mostly reliant upon opioids; however, long-term use of opioids is associated with multiple side effects. This review presents up-to-date developments in our understanding of the pathobiology of pain in SCD. To help focus future research efforts, major gaps in knowledge are identified regarding how sickle pathobiology evokes pain, pathways specific to chronic and acute sickle pain, perception-based targets of "top-down" mechanisms originating from the brain and neuromodulation, and how pain affects the sickle microenvironment and pathophysiology. This review also describes mechanism-based targets that may help develop novel therapeutic and/or preventive strategies to ameliorate pain in SCD.
| S-EPMC6142592 | biostudies-literature
Project description:Patients with sickle cell disease (SCD) suffer from intense pain that can start during infancy and increase in severity throughout life, leading to hospitalization and poor quality of life. A unique feature of SCD is vaso-occlusive crises (VOCs) characterized by episodic, recurrent, and unpredictable episodes of acute pain. Microvascular obstruction during a VOC leads to impaired oxygen supply to the periphery and ischemia reperfusion injury, inflammation, oxidative stress, and endothelial dysfunction, all of which may perpetuate a noxious microenvironment leading to pain. In addition to episodic acute pain, patients with SCD also report chronic pain. Current treatment of moderate to severe pain in SCD is mostly reliant upon opioids; however, long-term use of opioids is associated with multiple side effects. This review presents up-to-date developments in our understanding of the pathobiology of pain in SCD. To help focus future research efforts, major gaps in knowledge are identified regarding how sickle pathobiology evokes pain, pathways specific to chronic and acute sickle pain, perception-based targets of "top-down" mechanisms originating from the brain and neuromodulation, and how pain affects the sickle microenvironment and pathophysiology. This review also describes mechanism-based targets that may help develop novel therapeutic and/or preventive strategies to ameliorate pain in SCD.
| S-EPMC5709786 | biostudies-literature
Project description:Sickle cell disease (SCD) is a genetic disorder associated with hemolytic anemia, end-organ damage, reduced survival, and pain. One of the unique features of SCD is recurrent and unpredictable episodes of acute pain due to vasoocclusive crisis requiring hospitalization. Additionally, patients with SCD often develop chronic persistent pain. Currently, sickle cell pain is treated with opioids, an approach limited by adverse effects. Because pain can start at infancy and continue throughout life, preventing the genesis of pain may be relatively better than treating the pain once it has been evoked. Therefore, we provide insights into the cellular and molecular mechanisms of sickle cell pain that contribute to the activation of the somatosensory system in the peripheral and central nervous systems. These mechanisms include mast cell activation and neurogenic inflammation, peripheral nociceptor sensitization, maladaptation of spinal signals, central sensitization, and modulation of neural circuits in the brain. In this review, we describe potential preventive/therapeutic targets and their targeting with novel pharmacologic and/or integrative approaches to ameliorate sickle cell pain.
| S-EPMC6087885 | biostudies-literature
Project description:Sickle cell disease (SCD) is an inheritable hemoglobinopathy characterized by polymerization of hemoglobin S in red blood cells resulting in chronic hemolytic anemia, vaso-occlusive painful crisis, and multiorgan damage. In SCD, an increased reactive oxygen species (ROS) generation occurs both inside the red blood cells and inside the vascular lumen, which augment hemolysis and cellular adhesion. This review discusses the evolving body of literature on the role of ROS in the pathophysiology of SCD as well as some emerging therapeutic approaches to SCD with a focus on the reduction of ROS.
| S-EPMC6142561 | biostudies-literature
Project description:Pain is a complex multidimensional experience and the most common morbidity in patients with sickle cell disease (SCD). Tools to assess pain can be of use not only to guide pain treatment but also to provide insight into underlying pain neurobiology. Mechanisms of pain in SCD are multifactorial and are not completely elucidated. Although vaso-occlusion of microcirculation by sickled red cells is believed to be the underlying mechanism of acute vaso-occlusive pain, mechanisms for chronic pain and the transition from acute to chronic pain are under investigation. A number of modalities can be used in clinical practice and/or research to capture various dimensions of pain. Selection of a pain-assessment tool should be directed by the purpose of the assessment. Pain-assessment tools, many of which are currently in the early stages of validation, are discussed here. Development and validation of these multimodal tools is crucial for developing improved understanding of SCD pain and its management.
| S-EPMC6142608 | biostudies-other
Project description:Purpose: Frequencies of single nucleotide polymorphisms (SNPs) from pain related candidate genes are available for individuals with sickle cell disease (SCD). One of those genes, the arginine vasopressin receptor 1A gene (AVPR1A) and one of its SNPs, rs10877969, has been associated with pain and disability in other pain populations. In patients with SCD, clinical factors such as pain and stress have been associated with increased health care utilization, but it is not known if the presence of the AVPR1A SNP plays a role in this observation. The study purpose was to explore the relationships between rs10877969 and self-reported pain, stress, and acute care utilization events among individuals with SCD.Methods: In a cross-sectional investigation of outpatients with SCD, participants completed PAINReportIt®, a computerized pain measure, to describe their pain experience and contributed blood or saliva samples for genetic analysis. We extracted emergency department and acute care utilization from medical records.Results: The SNP genotype frequencies (%) for this sample were CC 30 (28%), CT 44 (41%), TT 33 (31%). Acute care utilization and stress as an aggravator of pain were significantly associated with the rs10877969 genotype (p = .02 and p = .002, respectively). The CT genotype had the highest mean utilization and CC genotype was associated with not citing stress as a pain aggravator. Chronic pain was not associated with rs10877969 (p = .41).Conclusion: This study shows that rs10877969 is related to indicators of stress and acute pain. Further research is recommended with other measures of stress and acute pain.
| S-EPMC6844466 | biostudies-literature
Project description:Sickle cell disease (SCD) is a genetic disorder causing painful and unpredictable Vaso-occlusive crises (VOCs) through blood vessel blockages. In this study, we propose explosive synchronization (ES) as a novel approach to comprehend the hypersensitivity and occurrence of VOCs in the SCD brain network. We hypothesized that the accumulated disruptions in the brain network induced by SCD might lead to strengthened ES and hypersensitivity. We explored ES's relationship with patient reported outcome measures (PROMs) as well as VOCs by analyzing EEG data from 25 SCD patients and 18 matched controls. SCD patients exhibited lower alpha frequency than controls. SCD patients showed correlation between frequency disassortativity (FDA), an ES condition, and three important PROMs. Furthermore, stronger FDA was observed in SCD patients with a higher frequency of VOCs and EEG recording near VOC. We also conducted computational modeling on SCD brain network to study FDA's role in network sensitivity. Our model demonstrated that a stronger FDA could be linked to increased sensitivity and frequency of VOCs. This study establishes connections between SCD pain and the universal network mechanism, ES, offering a strong theoretical foundation. This understanding will aid predicting VOCs and refining pain management for SCD patients.
| S-EPMC10973361 | biostudies-literature
Project description:Sickle cell disease (SCD) is a blood disorder with few treatment options currently available. However, in recent years, there has been much progress toward developing new therapies and curative treatments to help patients with SCD. Stem cell transplant remains the only approved curative treatment for SCD, but new clinical trials are being initiated using gene therapy and gene editing. We surveyed patients with sickle cell disease (N=9) about attitudes toward stem cell transplant, gene therapy to add a new healthy gene, gene editing to up-regulate fetal hemoglobin, or gene editing to correct the point mutation. The participants read a fact sheet that included objective information on each curative treatment. When asked which curative treatment each participant would choose, all four options were selected at least once. The most highly selected treatment was gene correction gene editing (N=4). Participants generally agreed that the four treatment options are beneficial but were more mixed in their thoughts on whether the options are dangerous. Reasons for selecting a particular curative treatment were variable, but the most selected reasons were perception of a cure (N=4) or decreased severity (N=4), and not needing a donor (N=4). We are at the beginning stages of understanding how patients with SCD make decisions about curative treatments. Currently, patients may be interested in any of the four possibilities for curative treatments, with gene correction gene editing as the most popular choice. Reasons for choosing one treatment over another are mixed.
| S-EPMC8799810 | biostudies-literature