The Pediatric Clinician's Evidence-based Strategies for Anticipatory Management and Treatment of Acute Pain at Home for Children and Adolescents with Sickle Cell Disease.

Guidelines for the management of the acute painful crisis in sickle cell disease.

Sickle cell disease is a genetic haemoglobin disorder affecting millions of people worldwide. Pain is one of the most commonly reported complication of sickle cell disease. Pain is further classified into two categories acute pain and chronic pain. Chronic pain is associated with more serious complications. Management of pain has a significant impact on quality of life of sickle cell disease patients. The purpose of this research is to review the available information about acute and chronic pain management in sickle cell disease. The best treatment for both acute and chronic pain requires a customized, varied approach. This approach combines therapeutic, non-pharmacological therapies, as well as integrated therapies as per the specific needs of each patient. Opioids are effectively used in management of the pain of sickle cell disease and their use is supported by literature especially in chronic pain. Methadone, ketamine, and nitrous oxide are also used to manage pain. For the treatment of acute pain, nonsteroidal anti-inflammatory medications, short-acting opioids, and adjuvants are used effectively in clinical practice. Opioids have become the recommended treatment for pain in sickle cell disease, and many chronic pain patients are sustained on opioid therapy for the rest of their lives. However, the distinction between acute and chronic opioid therapy modalities is blurred in sickle cell disease due to the association between recurring acute pain and chronic pain. Limited literature is available regarding management guidelines and therapeutic strategies so more clinical research and trials are needed in future to design and study effective management strategies for both acute and chronic pain.

Plasma-Based Inflammatory Signatures in Patients with Sickle Cell Disease during Baseline Health and Acute Pain

Neuropathic pain in individuals with sickle cell disease

Editorial I: Acute pain management: scientific evidence revisited

Presentation Date: 6/8/2024 Presentation Start Time: 6:00 PM Background Sickle cell disease (SCD), an inherited red cell disorder, generates abnormal (sickle) hemoglobin that polymerizes under hypoxic conditions. Sickle hemoglobin (HbS) polymerization produces sickled red blood cells (RBCs) and triggers vaso-occlusion and episodes of severe acute pain, also known as vaso-occlusive events (VOEs). These painful episodes are initiated by the adhesion of white blood cells (WBCs) to the endothelium via P-selectin, facilitating the binding of circulating sickle RBCs to WBCs. Subsequent polymerization of HbS within RBCs causes rigidity, leading to vessel occlusion and ischemia-induced pain. Concurrently, complement activation, a common pathogenic event in SCD, may exacerbate tissue damage and affect multiple cell types (RBCs, leukocytes, and endothelial cells), thereby also contributing to pain. Painful VOEs represent a hallmark complication of sickle cell disease (SCD) in adolescents and adults, often leading patients to seek medical care in hospital emergency departments. Despite advances in pain management, current SCD therapies lack effectiveness in modifying the course of VOE once initiated, leaving many patients with inadequate or incomplete treatment. Consequently, there is a pressing need for non-opioid-based therapeutic options that target the underlying mechanisms of VOE to provide more comprehensive pain relief and improve patient outcomes. We propose to prevent VOE pain by reducing the inciting event of WBC adhesion via P-selectin to the endothelium and reducing complement activation. IHP-102, a glycan-based therapeutic, targets multiple VOE-related mechanisms, including P-selectin and complement, and has been demonstrated to reduce pulmonary vessel occlusion in humanized SCD mice. This study aims to evaluate the analgesic efficacy of IHP-102 to reduce acute VOE-like pain behaviors in the Townes humanized SCD mouse model. Methods Acute dose-response and longitudinal studies of IHP-102 will be conducted in Townes SS (SCD) and AA (control) mice. Both male and female mice (8 weeks old) will be utilized to explore potential sex-related effects. Acute VOE will be induced by hypoxia (5-15% O2) exposure and IHP-102 (0-60 mg/kg, subcutaneous, s.c.) will be administered at onset of reoxygenation. Behavioral (pain) testing for mechanical and thermal (hot & cold) hypersensitivity, as well as grip strength will occur 2-3 hours post-injection/exposure. In a longitudinal study, IHP-102 (30 mg/kg, effective dose for preventing vaso-occlusion) or the lowest effective dose will be administered daily for two weeks, with hypoxia exposure and behavioral testing every 3 days. After the final testing, mice will be euthanized, and blood/organs collected for biomarker analysis, including an assessment of organ damage. The impact of IHP-102 on cellular adhesion to a P-selectin-lined microfluidics device will be evaluated. Data analysis will involve ANOVAs and linear mixed models, reporting regression coefficients, standard errors, and 95% confidence intervals. Results We anticipate that IHP-102 will significantly decrease acute and chronic pain behaviors in SS mice treated with IHP-102 compared to untreated controls, by reducing vaso-occlusion via P-selectin. We anticipate that targeting of complement activation will further contribute to pain reduction by mitigating tissue damage and inflammation associated with VOEs. By modulating complement-mediated pathways, we expect to observe improvements in vascular integrity and reduced leukocyte infiltration, leading to a decrease in overall ischemia-induced pain. Conclusions If successful in this pre-clinical animal model, IHP-102 will progress to human clinical trials. Conceptually, IHP is a game changing medication for SCD as current home treatment options are limited to non-specific anti-inflammatory and opioid medications. IHP-102 can be administered subcutaneously by individuals with SCD in their home, preventing further adhesion and vaso-occlusion in a disease-targeted manner, and reducing pain, opioid exposure, and need for hospitalization. Overall, we anticipate that the results of this study will provide valuable insights into the therapeutic potential of IHP-102 in alleviating acute VOE-like pain behaviors, offering a promising avenue for improving pain management and enhancing the quality of life for individuals with SCD.

Observed Variability in Gene Expression in Individuals with Sickle Cell Disease during Baseline Health and Acute Pain

Advancing Care of Patients with Sickle Cell Disease through a Transformative Quality Improvement Initiative

Controlled-release opioids cause harm and should be avoided in management of postoperative pain in opioid naïve patients

Acetaminophen plus a nonsteroidal anti-inflammatory drug decreases acute postoperative pain more than either drug alone

Pain is a common complication of sickle cell disease. Sickle cell pain can often be effectively managed by pediatricians in outpatient and hospital settings. Acute pain management should be initiated quickly. Patients need to be evaluated for sickle cell complications and other causes of pain. Nonsteroidal anti-inflammatory drugs and opioids are the mainstay of pain treatment, but additional therapies include hydration, local pain control, muscle relaxants, and nonpharmacologic approaches. Healthy lifestyle habits and good behavioral and mental health are important for preventing and coping with sickle cell disease pain. Disease-modifying therapies, such as hydroxyurea, can help prevent sickle hemoglobin polymerization and acute pain episodes. Because sickle cell disease largely affects people who are racialized minorities in the United States, health-care providers need to be aware of how their own personal biases may affect care of these patients.

Pklr Is a Genetic Modifier of Sickle Cell Disease

Pain is the most common complication of Sickle Cell Disease (SCD). Tissue oximetry properties in SCD during steady state and acute pain are not well described. This was a cross sectional study of tissue oximetry properties in individuals with SCD during steady state, acute pain and healthy controls without SCD. A novel tissue oximetry device was used to better account for tissue pigmentation interference. We hypothesized that during acute SCD pain, blood volume to painful areas would be at least 10% less than steady state. Bayesian analyses of the data (with flat piors) were planned a priori because of the small projected sample size. The sample included 14 individuals (4 during crisis, 5 steady state, and 5 controls). In individuals with SCD, blood volume to the lower back was higher during crisis (0.18% of tissue volume vs. 0.14% ). Bayesian analyses yielded a 3% probability that our hypothesis (that blood volume would decrease by 10% ) was correct. During acute SCD pain, blood volume to painful areas is not decreased. Bayesian analyses were useful for interpretation of small sample data and may have utility in early phase trials for rare diseases.

Sickle cell disease is an inherited genetic disorder characterized by an abnormality of haemoglobin that predisposes to polymerization and consequent deformation ("sickling"). Sickle cell disease can cause episodes of acute severe pain. Chronic pain may also occur. Currently, pain is inadequately managed. The primary aim of the review was to assess the effectiveness of pharmacological analgesic interventions for pain management in sickle cell disease, including the treatment of acute and chronic pain in children and adults. A pre-defined search strategy was used to electronically search the MEDLINE and EMBASE databases. Searches were also conducted on the Cochrane Controlled Trial Register (CCTR) and the Oxford pain randomised controlled trials citation database. The search period covered from January 1965 through to June 2002. Bibliographies of retrieved studies were searched for additional references. No language restriction was used. All randomised controlled trials involving pharmacological treatment of acute or chronic pain in children or adults with sickle cell disease were selected. Patients with haemoglobin SS, haemoglobin S ss thalassaemia and the haemoglobin SC group were included. Trials were quality rated using the Oxford quality scale. Continuous measures of outcome were combined using weighted mean differences. Overall effect size was calculated with 95% confidence intervals. Nine randomised controlled trials were identified. All studies involved small numbers of patients with acute sickle cell pain only. Interventions included NSAIDs (versus placebo in four studies; versus strong opioids in one study), strong opioids (oral versus parenteral in one study; morphine versus alternate in one study) and corticosteroids (versus placebo in two studies). Lack of data, small patient numbers, variations in study design and outcome measures limited the review. Due to heterogeneity of methodologies and reporting, it was not possible to perform meaningful meta-analyses. There were no studies addressing chronic pain in sickle cell disease. There is limited evidence for analgesic interventions in acute pain crises. Studies have been under-powered. There is not enough data for inter-trial comparisons. In one trial, there was no difference in the efficacy of sustained-release oral versus parenteral morphine, which suggests that oral morphine should be considered for acute pain. Parenteral corticosteroids appear to shorten the period over which analgesics are required and hospital length-of-stay, without producing short-term major adverse effects. More research is needed to improve pain management in sickle cell disease.

Pain management for sickle cell disease