Sickle Cell Pain: Biology, Etiology, and Treatment

Ballas, Samir K.; Eckman, James R.

doi:10.1017/cbo9780511596582.028

Cited by 6 publications

(8 citation statements)

References 192 publications

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“…For CYP3A, UGT2B7, and ABCB1, the most likely haplotypes were determined with the Phase 2.1.1. software [5] (available from: http://stephenslab.uchicago.edu/software.html). A potent oral P-selectin blocking agent improves microcirculatory blood flow and a marker of endothelial cell injury in patients with sickle cell disease Abdullah Kutlar, 1 * Kenneth I. Ataga, 2 Lillian McMahon, 3 Joanna Howard, 4 Frederic Galacteros, 5 Ward Hagar, 6 Elliott Vichinsky, 6 Anthony T.W. Cheung, 7 Neil Matsui, 8 and Stephen H. Embury 8…”

Section: Methodsmentioning

confidence: 99%

“…Most notably, occlusion of flow in the microvasculature causes the acute pain crises [3] that are the commonest cause for patients with SCD to seek medical attention [4] and major determinants of their quality of life [5]. Based on evidence that endothelial P-selectin is central to the abnormal blood flow in SCD we provide results from four of our studies that are germane to microvascular blood flow in SCD.…”

Section: Methodsmentioning

confidence: 99%

“…Much of sickle cell disease (SCD) morbidity is due to recurrent painful crises mainly treated by codeine and morphine. However, surprisingly, there are no genotypic data that relate to the frequency of the main opiate-related SNPs in SCD populations [4]. One may argue that the allelic frequencies for African-Americans (AA) are known and that, since SCD patients are mostly of AA origins, their allelic frequencies should be the same.…”

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confidence: 99%

“…As a consequence, given the very large number of potential genotype combinations, it is likely that very large sample sizes are necessary to draw conclusions and that these studies will be conducted in the general population first. Nevertheless, we believe that SCD populations should also be studied separately given the specificity of sickle cell pain which cannot be compared to any other one [4].…”

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confidence: 99%

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Genotypic screening of the main opiate‐related polymorphisms in a cohort of 139 sickle cell disease patients

Joly¹,

Gagnieu²,

Bardel³

et al. 2012

American J Hematol

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10. Ko M, Huang Y, Jankowska AM, et al. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Much of sickle cell disease (SCD) morbidity is due to recurrent painful crises mainly treated by codeine and morphine. However, surprisingly, there are no genotypic data that relate to the frequency of the main opiate-related SNPs in SCD populations [4]. One may argue that the allelic frequencies for African-Americans (AA) are known and that, since SCD patients are mostly of AA origins, their allelic frequencies should be the same. Obviously, this remark is true but we thought it was important to consider the particular subgroup of SCD patients to ensure that some SNPs were not under-or over-represented because of a founder effect. We, thus, decided to perform, in a cohort of 139 SCD patients, a quite extensive genotyping of these SNPs (Table I) with a haplotypic interpretation for those located on the same locus (Table II).Codeine is a pro-drug inactive by itself until it is metabolized into morphine by the CYP2D6 pathway. After oral or parenteral administration, morphine is partially metabolized by the CYP3A pathway (CYP3A4 and CYP3A5 genes) and by the UGT2B7 enzyme. Independently, an increased ABCB1 activity (a well-known drug efflux protein) is also expected to decrease the bioavailability of both morphine (brain efflux) and codeine (gut efflux) [10]. Very logically, the most frequent polymorphisms that modify the enzymatic activity were chosen for each pathway. For the CYP3A pathway, we genotyped two SNPs associated with a lower CYP3A activity: rs2740574 (A-392G 5 *1B allele) on the CYP3A4 gene (wild-type *1A) and rs776746 (A6986G 5 *3 allele) on the CYP3A5 gene (wild-type *1) [11]. For the UGT2B7 gene, we genotyped two SNPs associated with a lower glucuronidation of morphine and codeine: rs7438135 (A-840G) and rs73823859 (G-79A) [12,13]. For the CYP2D6 gene, we searched: (i) two polymorphisms associated with a null activity: rs892097 (G1846A 5 *4 allele) and the whole gene deletion (*5 allele), (ii) a SNP associated with an intermediate activity and very prevalent in the African population: rs28371706 (C1023T 5 *17 allele), and (iii) a gene duplication associated with an enhanced activity [8,14]. For the ABCB1 gene, we genotyped three SNPs associated with a variation (decrease or increase) of the efflux activity for many drugs: rs1128503 (C1236T) on exon 12, rs2032582 (G2677T) on exon 21 and rs1045642 (C3435T) on exon 26 [15]. Interestingly, the mutant T nucleotide for rs1045642 has been associated with a better morphine pain relief in two independent studies [16,17]. By taking these three SNPs together, some authors have defined the three main ABCB1 haplotypes [6,7]: (i) the *1 allele (C/G/C) which is the wild-type allele, (ii) the *2 allele (T/T/T), and (iii) the *2Kr allele (C/G/T).Two SNPs are mainly responsible for a lower analgesic effect of opioids. The most important one is A118G (Asn40Asp-rs1799971) on the OPRM1 gene [1,18], and the second one is G322A (Val158Met-rs4680) on the C...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Genotypic screening of the main opiate‐related polymorphisms in a cohort of 139 sickle cell disease patients

Joly¹,

Gagnieu²,

Bardel³

et al. 2012

American J Hematol

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“…9 Contributing factors are variable and may include avascular necrosis of joints, bone infarction, leg ulcers, osteomyelitis, and central and peripheral sensitization. [10][11][12] In a daily diary study, 54% of adolescents and adults with SCD reported having pain 51% of the time and 29% reported pain almost daily. 13 In a review study of adults with SCD, chronic pain ranged from 29-100% across seven studies, with a weighted mean of 65%.…”

Section: Introductionmentioning

confidence: 99%

A Qualitative Study of Chronic Pain and Self-Management in Adults with Sickle Cell Disease

Matthie

Ross

Sinha

et al. 2019

Journal of the National Medical Association

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Acute, intermittent vaso-occlusive pain is the hallmark of sickle cell disease (SCD) and is associated with substantial morbidity and impaired quality of life (QOL). The subgroup of adults with SCD who transition from recurrent, acute pain to chronic, persistent pain have even greater QOL impairment and higher rates of healthcare utilization. Self-management is central to SCD management; however, its role in chronic pain management is not established. This qualitative study was conducted to answer the following research questions: (1) What is the chronic pain experience of adults with SCD? (2) What self-management strategies do adults with SCD use for chronic pain? and (3) Do adults with SCD have any needs in the self-management of chronic pain? Eighteen Black adults with SCD completed a demographics questionnaire and an interview. The majority of the participants were 21-30 years of age (mean 33.5, SD 7.6), female (61.1%), employed at least part-time (61.1%), single/never married (72.2%), and had a SCD type of sickle cell anemia (55.5%). Interview analysis revealed three major themes: (1) the chronic pain experience; (2) strategies for managing chronic pain; and (3) challenges and needs in managing chronic pain. Study findings can be used to support chronic pain management among adults with SCD. Further research is needed to devise and implement effective strategies for the prevention and management of chronic SCD pain.

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Prevalence and predictors of chronic pain intensity and disability among adults with sickle cell disease

Matthie

Jenerette

Gibson

et al. 2020

Health Psychology Open

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Among 170 adults with sickle cell disease, we evaluated chronic pain impact and disability prevalence, assessed age and gender differences, and identified psychosocial predictors of chronic pain intensity and disability. Most participants had a high level of disability. Chronic pain intensity and disability were significantly associated with pain catastrophizing and chronic pain self-efficacy, and worsened with age. Further research is needed to confirm study findings and develop interventions, including palliative care approaches that address catastrophizing and disability, particularly for young women and middle-aged adults with sickle cell disease. Moreover, consistent clinical assessment of chronic pain and psychosocial health should be implemented.

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Sickle Cell Pain: Biology, Etiology, and Treatment

Cited by 6 publications

References 192 publications

Genotypic screening of the main opiate‐related polymorphisms in a cohort of 139 sickle cell disease patients

Genotypic screening of the main opiate‐related polymorphisms in a cohort of 139 sickle cell disease patients

A Qualitative Study of Chronic Pain and Self-Management in Adults with Sickle Cell Disease

Prevalence and predictors of chronic pain intensity and disability among adults with sickle cell disease

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