Chemokine (c-c motif) receptor 2 mediates mechanical and cold hypersensitivity in sickle cell disease mice

Approximately one-third of individuals with sickle cell disease (SCD) develop chronic pain. This debilitating pain is inadequately treated because the underlying mechanisms driving the pain are poorly understood. In addition to persistent pain, patients with SCD are also in a tonically proinflammatory state. Previous studies have revealed that there are elevated plasma levels of many inflammatory mediators including chemokine (c-c motif) ligand 2 (CCL2) in individuals with SCD. Using a transgenic mouse model of SCD, we investigated the contributions of CCL2 signaling to SCD-related pain. Inhibition of chemokine receptor 2 (CCR2), but not CCR4, alleviated the behavioral mechanical and cold hypersensitivity in SCD. Furthermore, acute CCR2 blockade reversed both the behavioral and the in vitro responsiveness of sensory neurons to an agonist of TRPV1, a neuronal ion channel previously implicated in SCD pain. These results provide insight into the immune-mediated regulation of hypersensitivity in SCD and could inform future development of analgesics or therapeutic measures to prevent chronic pain.
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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Until recent findings that sickle cell disease (SCD) pain has characteristics consistent with central or peripheral sensitization,12,27,28,43 it was typically viewed as acute or persistent pain and treated mostly with opioids. Often the etiology of SCD pain is thought to be only episodic, driven by vaso-occlusion and somatic or visceral tissue damage,1,2,4 however, it has become increasingly clear that adults with SCD also experience chronic pain. A growing body of evidence now supports,12,27,28,40,43, but is not conclusive, that sensitization contributes to chronic pain in some adults with SCD.
Source: The Journal of Pain - Category: Materials Science Authors: Source Type: research
Inherited hemoglobin disorders, including beta-thalassemia (BT) and sickle-cell disease (SCD) are the most common monogenic diseases worldwide, with a global carrier frequency of over 5%. With migration they are becoming more common worldwide, making their management and care an increasing concern for health care systems.BT is characterized by an imbalance in the α/β-globin chain ratio, ineffective erythropoiesis, chronic hemolytic anemia, and compensatory haemopoietic expansion. Globally, there are over 25,000 births each year with transfusion-dependent thalassemia (TDT). The current available tr...
Source: Mediterranean Journal of Hematology and Infectious Diseases - Category: Hematology Source Type: research
This study was aimed to identify the predictors of splenic sequestration crisis (SSC) among pediatric patients with sickle cell disease (SCD).This prognosis study was carried out in the pediatric immuno-hematology unit, over 20 years (1998 to 2017), enrolling patients with SCD. The cox model was used in multivariate analysis.Among 423 patients with SCD (240 S/S phenotype, 128 S/B0, 30 S/B+, 14 S/O arab and 11 S/C), 150(35.4%) had at least one episode of SSC. The average age of patients at the first episode was 48.3 months ± 32.4(2–168). Recurrence of SSC was observed in 117 patients (78%). Spleen size ≥...
Source: Blood Cells, Molecules, and Diseases - Category: Hematology Source Type: research
Sickle cell disease (SCD) is one of the most prevalent genetic conditions in sub-Saharan Africa. It is a chronic, lifelong disease often characterized by severe pain. However, SCD has received little investment terms of health research, though there is currently a growing pool of SCD data from health and research facilities in different countries. To facilitate research on SCD in Africa, the SickleInAfrica consortium has established a SickleInAfrica registry. The registry will store a systematic collection of longitudinal data from persons with SCD across sub-Saharan Africa, and currently, participants are being enrolled i...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Publication date: Available online 5 October 2019Source: Neuroscience LettersAuthor(s): Patrick CarrollAbstractSickle cell disease is a uniquely complex painful disease, with lifelong episodes of unpredictable acute pain and superimposed chronic pain in adulthood. Both painful crises and chronic pain in sickle cell disease lack strong objective pathological correlates and their mechanisms are poorly understood. Opioids have emerged as the standard of care for severe acute pain in sickle cell disease and many patients with chronic pain are maintained on chronic opioid therapy. The strong association between recurrent acute ...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
by Drew Rosielle (@drosielle)A Series of Observations on Opioids By a Palliative Doc Who Prescribes A Lot of Opioids But Also Has Questions.This is the 5th post in a series about opioids, with a focus on how my thinking about opioids has changed over the years. See also:Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.Part 2 – We Were Wrong 20 years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid DosesPart 3 – Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Ano...
Source: Pallimed: A Hospice and Palliative Medicine Blog - Category: Palliative Care Tags: cancer opioids pain rosielle The profession Source Type: blogs
by Drew Rosielle (@drosielle)A Series of Observations on Opioids By a Palliative Doc Who Prescribes A Lot of Opioids But Also Has Questions.This is the 5th post in a series about opioids, with a focus on how my thinking about opioids has changed over the years. See also:Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.Part 2 – We Were Wrong 20 years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid DosesPart 3 – Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Ano...
Source: Pallimed: A Hospice and Palliative Medicine Blog - Category: Palliative Care Tags: opioid pain rosielle The profession Source Type: blogs
Purpose of review Red cell transfusions are one of the most common and important therapies used for patients with sickle cell disease (SCD). For prevention of strokes, there is abundant evidence that transfusions are efficacious, whereas for other indications, such as prevention of pain, there are less data. Nonetheless, with few therapeutic options, the use of transfusion for prevention of acute pain has increased in children and adults with SCD without a clear understanding of its benefits. Recent findings Although it makes conceptual sense that red cell transfusions would prevent pain that arises from vaso-occlusio...
Source: Current Opinion in Hematology - Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research
After 36 agonizing years with sickle cell disease, Tesha Samuels is in complete remission — free, at least for now, of one of the most painful disorders known to medicine. Yet Samuels's body still hurts almost every day.The question that perplexes her doctors at the National Institutes of Health is why, after her blood disorder has been vanquished, she is still in pain.Perhaps her newly healed red blood cells are not yet bringing enough oxygen to her tissues. Perhaps the emotional toll of a lifetime of constant pain has left her prepared to feel little else. Or perhaps the pain signals that have flooded her brain...
Source: Psychology of Pain - Category: Anesthesiology Source Type: blogs
Discussion Our study is the first to examine the association between MPQ sensory pain quality descriptors and QST-derived classifications in adults with SCD. Our findings provide the basis for the development of a MPQ subscale with potential as a mechanism-based screening tool for neuropathic pain.
Source: Nursing Research - Category: Nursing Tags: FEATURE ARTICLES Source Type: research
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