scholarly journals Characterization of Neuropathic Pain in Sickle Cell Disease

2017 ◽  
Author(s):  
M Nalbandian ◽  
H Kyotakoze ◽  
H Kaminsky ◽  
D Keleny ◽  
P Baghdasaryan ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease

scholarly journals Characterization of Neuropathic Pain in Sickle Cell Disease

2017 ◽  
Author(s):  
M Nalbandian ◽  
H Kyotakoze ◽  
H Kaminsky ◽  
D Keleny ◽  
P Baghdasaryan ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease

Health-related quality of life and neuropathic pain in sickle cell disease in Jamaica

2021 ◽  
pp. 101107
Author(s):  
Rachel Bartlett ◽  
Zachary Ramsay ◽  
Amza Ali ◽  
Justin Grant ◽  
Angela Rankine-Mullings ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Neuropathic Pain ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Health Related Quality ◽  
Cell Disease ◽  
Related Quality ◽  
Health Related

scholarly journals Neuropathic Pain in Children with Sickle Cell Disease: The Hidden Side of the Vaso-Occlusive Crisis

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 84
Author(s):  
Jeanne Sigalla ◽  
Nathalie Duparc Alegria ◽  
Enora Le Roux ◽  
Artemis Toumazi ◽  
Anne-Françoise Thiollier ◽  
...  
Keyword(s):  
Risk Factors ◽  
Neuropathic Pain ◽  
Sickle Cell Disease ◽  
Sex Ratio ◽  
Prospective Study ◽  
Sickle Cell ◽  
Clinical Presentation ◽  
Early Stage ◽  
Cell Disease ◽  
A Prospective Study

The majority of hospitalizations of patients with sickle cell disease (SCD) are related to painful vaso-occlusive crises (VOCs). Although the pain of VOC is classically nociceptive, neuropathic pain (NP) has also been demonstrated in SCD patients. The aim of our study is to specify the prevalence of NP during VOCs in SCD children using a dedicated scale and to measure its characteristics. We performed a prospective study that included SCD children hospitalized for an acute VOC. The presence of NP was sought with the DN4 scale on the second and fourth days of hospitalization. A total of 54 SCD children were included in the study. Overall, 41% of the patients (n = 22) experienced neuropathic pain during the VOC, mostly at an early stage (Day 2). The median age, the sex ratio, the location of the pain, and the morphine consumption were similar for patients with and without NP. Our study shows that neuropathic pain is very common during VOCs in SCD children. The absence of identified risk factors should prompt us to be vigilant regardless of the patient’s age, sex, and clinical presentation.

scholarly journals Electrical Impedance Characterization of Erythrocyte Response to Cyclic Hypoxia in Sickle Cell Disease

ACS Sensors ◽  
2019 ◽  
Vol 4 (7) ◽  
pp. 1783-1790 ◽  
Author(s):  
Jia Liu ◽  
Yuhao Qiang ◽  
Ofelia Alvarez ◽  
E Du
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Electrical Impedance ◽  
Cell Disease ◽  
Impedance Characterization

scholarly journals Engineering, Generation and Preliminary Characterization of a Humanized Porcine Sickle Cell Disease Animal Model

2020 ◽  
Author(s):  
Tobias M. Franks ◽  
Sharie J. Haugabook ◽  
Elizabeth A. Ottinger ◽  
Meghan S. Vermillion ◽  
Kevin M. Pawlik ◽  
...  
Keyword(s):  
Animal Model ◽  
Sickle Cell Disease ◽  
Mouse Models ◽  
Sickle Cell ◽  
Cell Model ◽  
Globin Genes ◽  
Cell Disease ◽  
Small Vessels

AbstractMouse models of sickle cell disease (SCD) that faithfully switch from fetal to adult hemoglobin (Hb) have been important research tools that accelerated advancement towards treatments and cures for SCD. Red blood cells (RBCs) in these animals sickled in vivo, occluded small vessels in many organs and resulted in severe anemia like in human patients. SCD mouse models have been valuable in advancing clinical translation of some therapeutics and providing a better understanding of the pathophysiology of SCD. However, mouse models vary greatly from humans in their anatomy and physiology and therefore have limited application for certain translational efforts to transition from the bench to bedside. These differences create the need for a higher order animal model to continue the advancement of efforts in not only understanding relevant underlying pathophysiology, but also the translational aspects necessary for the development of better therapeutics to treat or cure SCD. Here we describe the development of a humanized porcine sickle cell model that like the SCD mice, expresses human ɑ-, β− and γ-globin genes under the control of the respective endogenous porcine locus control regions (LCR). We also describe our initial characterization of the SCD pigs and plans to make this model available to the broader research community.

scholarly journals Zinc Finger Nuclease-Mediated Disruption of the BCL11A Erythroid Enhancer Results in Enriched Biallelic Editing, Increased Fetal Hemoglobin, and Reduced Sickling in Erythroid Cells Derived from Sickle Cell Disease Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 974-974 ◽  
Author(s):  
Samuel Lessard ◽  
Pauline Rimmele ◽  
Hui Ling ◽  
Kevin Moran ◽  
Benjamin Vieira ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Cell Therapy ◽  
Single Cell ◽  
Zinc Finger ◽  
Sickle Cell ◽  
Fetal Hemoglobin ◽  
Cell Disease ◽  
Hematopoietic Stem ◽  
Potential Efficacy

High fetal hemoglobin (HbF) levels are associated with decreased severity and mortality in sickle cell disease (SCD) and beta thalassemia (BT). We have developed a novel gene-edited cell therapy using autologous hematopoietic stem and progenitor cells (HSPCs) that have been genetically modified with zinc finger nucleases (ZFNs) to reactivate HbF expression. The ZFNs target the binding motif of GATA1 (GATAA) within an intronic erythroid-specific enhancer (ESE) of BCL11A, which encodes a major transcriptional repressor of HbF. Previously, we reported successful ZFN-mediated editing of the BCL11A ESE and reactivation of HbF in both dual (granulocyte colony-stimulating factor (G-CSF) and plerixafor) and single plerixafor mobilized HSPCs(Holmes 2017, Moran 2018). Both related drug candidates, ST-400 and BIVV003, are currently in phase 1/2a clinical trials for transfusion-dependent BT (NCT03432364) and SCD (NCT03653247), respectively. Here, we performed extensive genetic and phenotypic characterization of ZFN-edited HSPCs from healthy and SCD donors. We performed single-cell characterization of BCL11A ESE-edited HSPCs from 4 healthy donors. Briefly, individual HSPCs were sorted and cultured in erythroid differentiation medium. Genomic DNA and protein lysate were collected at day 14 and 20, respectively. In total, we successfully genotyped 961 single-cell derived colonies by next-generation sequencing. The distribution was highly skewed towards biallelic-edited cells (P<3x10-149) representing 94% of edited clones, suggesting that ZFN-expressing cells are likely to become edited at both alleles. We found that each edited allele contributed additively to an increase in HbF% of 15% (P=1x10-80) as measured by UPLC. Clones harboring GATAA-disrupting indels on both alleles displayed on average 34% more HbF% than WT clones (P=1x10-112). In contrast, clones with biallelic indels that left the motif intact displayed a more modest increase (13%, P=1x10-6). Overall, our data revealed that >90% of edited cells were biallelic, displaying on average 27-38% more HbF% despite variation in donor baseline levels. We observed a strong enrichment of biallelic-edited homozygotes (same indel pattern at both alleles) compared to an expected random distribution (161 vs 24; P<1x10-5). These clones may harbor larger deletions not captured by sequencing, as reported previously using CRISPR/Cas9 (Kosicki 2018). To address this question, we used a combination of a small amplicon sequencing assay design covering an informative SNP and a 12kb amplicon Nextera assay. We found that 27% of initially assigned homozygote clones were bona fide homozygotes (44/161) with the remaining harboring indels not originally captured. Nevertheless, most indels remained small, with 91% of indels <50bp, and deletions and insertions >1kb together consisting of less than 1% of alleles. The largest deletion was 4kb, but no indel extended outside the enhancer region of BCL11A or altered the coding region (>26 kb away). Moreover indels >50bp were not associated with enucleation levels (P=0.77), suggesting that they did not alter erythroid function. Overall, these results are consistent with previous data showing that ZFN-mediated gene editing does not impair HSPC function in vitro based on colony forming unit (CFU) production, and that injection of BIVV003 into immune-deficient NBSGW mice results in robust long-term engraftment with no impact on the number of HSPCs or their progeny, including erythrocytes. Finally, BCL11A ESE editing in HSPCs mobilized from one SCD donor resulted in a 3-fold HbF increase consistent across technical duplicates, without impacting CFU production or erythroid enucleation. Importantly, clonal analysis revealed a similar enrichment of biallelic editing (P=6x10-4) and additive HbF up-regulation, with biallelic edited cells reaching 28% more HbF% than unedited cells (50% vs 22%, P=7x10-5). Furthermore, enucleated cells differentiated from edited HSPCs showed attenuation of sickling under hypoxic conditions supporting the potential efficacy of BIVV003. Experiments in HSPCs from additional SCD donors are ongoing. Overall, our data have shown that ZFN-mediated disruption of BCL11A ESE results in enriched biallelic editing with on-target small indels, reactivates HbF and reduces sickling, supporting the potential efficacy and specificity of BIVV003 as a novel cell therapy for SCD. Disclosures Lessard: Sanofi: Employment. Rimmele:Sanofi: Employment. Ling:Sanofi: Employment. Moran:Sanofi: Employment. Vieira:Sanofi: Employment. Lin:Sanofi: Employment. Hong:Sanofi: Employment. Reik:Sangamo Therapeutics: Employment. Dang:Sangamo Therapeutics: Employment. Rendo:Sanofi: Employment. Daak:Sanofi: Employment. Hicks:Sanofi: Employment.

scholarly journals Impact of neuropathic pain on quality of life in adults with sickle cell disease: observational study

2020 ◽  
Author(s):  
Lismar Fernando Oliveira dos Santos ◽  
Milenna Wild Guimarães ◽  
Abrahão Fontes Baptista ◽  
Katia Nunes Sá
Keyword(s):  
Quality Of Life ◽  
Neuropathic Pain ◽  
Sickle Cell Disease ◽  
Observational Study ◽  
Sickle Cell ◽  
Cell Disease

scholarly journals Neuropathy, neuropathic pain, and sickle cell disease

2013 ◽  
Vol 88 (11) ◽  
pp. 927-929 ◽  
Author(s):  
Samir K. Ballas ◽  
Deepika S. Darbari
Keyword(s):  
Neuropathic Pain ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease

Neuropathic Vs. Nociceptive Pain in Adolescent Sickle Cell Disease (SCD) Evaluated by a Computer-Based Self-Assessment Pain Tool.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2576-2576 ◽  
Author(s):  
Richard J. Labotka ◽  
Robert E. Molokie ◽  
A. Kyle Mack ◽  
Alexis A Thompson ◽  
Young Ok Kim ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
The Body ◽  
Nociceptive Pain ◽  
Mcgill Pain Questionnaire ◽  
Cell Disease ◽  
Self Assessment ◽  
Body Segments ◽  
Computer Based

Abstract Abstract 2576 Poster Board II-553 Pain remains the most frustrating and debilitating symptom of sickle cell disease (SCD). Yet, because pain is a perception of a sensation, objective assessment of pain remains elusive. In order to achieve adequate pain control, it is imperative that the patient be able to effectively communicate with the physician regarding the extent, severity and quality of the pain, as well as the response of the pain to the therapeutic intervention. Moreover, SCD pain may have two components, nociceptive (due to organ/tissue injury) and neuropathic (due to somatosensory system lesion or disease), with differing pathophysiologies, and differing responses to pain medications. PAINReportIt® is a multi-dimensional computerized, self-assessment pain reporting tool based on the McGill Pain Questionnaire (MPQ). The MPQ has been validated for adolescents and adults. However, the PAINReportIt®, which was developed originally for the evaluation of cancer pain, has not previously been used in adolescents, nor in the study of adolescents' SCD pain. The purpose of this study was to examine the frequency with which pain experienced in various body areas by adolescents and young adults had characteristics consistent with nociceptive and neuropathic pain. Methods. Inclusion criteria included an SCD diagnosis (SS, SC or S-beta thal) and age at least 14 years. Patients attending two pediatric/adolescent comprehensive sickle cell clinics were invited to participate. Consenting subjects were first instructed and then allowed to complete the PAINReportIt® tool, in which they marked their painful sites on a graphic body outline, selected pain quality descriptors from word lists provided by the computer, and for each site they matched each site to the pain quality descriptors that represented the site. The descriptors included sensory descriptors that are known to be characteristic of either neuropathic pain or nociceptive pain. Results. PAINReportIt® tools were completed by 49 SCD subjects, whose ages ranged from 14 to 27 years (mean, 18 +/− 2.6 years). For analysis, the body was divided into nine segments, and the computer analyzed the marked painful body outline sites and identified the body segments involved. Descriptive statistics were used to determine the frequency for which each body segment included a painful site, and the frequencies for which that site was characterized as having neuropathic or nociceptive pain qualities, or both. These results are summarized in the Table below. As the Table shows, virtually all body segments were frequently involved with pain, the upper back and legs being the most frequently reported, and the lower back the least (Column 1). For body segments reported as painful, few were reported as having only nociceptive (Column 2) or neuropathic (Column 3) pain qualities. The majority of painful sites were described by subjects as having mixed pain qualities (Column 4). As Column 5 shows, from 76% to 100% of all painful sites were characterized as having a neuropathic pain component. When the number of descriptors associated with each site was reviewed (data not shown), the right leg was matched to the largest number of neuropathic descriptors (Aching, Burning, Cold, Drilling, Flickering, Numb, Penetrating, Radiating, Shooting, Spreading, Tight, Tingling). The upper back was matched to the largest number of nociceptive descriptors (Beating, Cramping, Crushing, Gnawing, Hurting, Piercing, Pounding, Pressing, Pulsing, Sharp, Sore, Splitting, Squeezing, Tender, Throbbing). Conclusions. When utilizing a computer-based self-reporting pain tool, SCD patients overwhelmingly describe a neuropathic component to their pain as well as a nociceptive component. The high frequency of neuropathic pain has been underappreciated, and this may contribute to the difficulty in managing sickle cell pain, since this pain component is not well controlled by opioid analgesics. Disclosures: No relevant conflicts of interest to declare.

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