Amanda M. Brandow

Transient receptor potential vanilloid 1 mediates pain in mice with severe sickle cell disease.

Pain is the leading cause of emergency department visits, hospitalizations, and daily suffering in individuals with sickle cell disease (SCD). The pathologic mechanisms leading to the perception of pain during acute RBC sickling episodes and development of chronic pain remain poorly understood and ineffectively treated. We provide the first study that explores nociceptor sensitization mechanisms that contribute to pain behavior in mice with severe SCD. Sickle mice exhibit robust behavioral hypersensitivity to mechanical, cold, and heat stimuli. Mechanical hypersensitivity is further exacerbated when hypoxia is used to induce acute sickling. Behavioral mechanical hypersensitivity is mediated in part by enhanced excitability to mechanical stimuli at both primary afferent peripheral terminal and sensory membrane levels. In the present study, inhibition of the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1) with the selective antagonist A-425619 reversed the mechanical sensitization at both primary afferent terminals and isolated somata, and markedly attenuated mechanical behavioral hypersensitivity. In contrast, inhibition of TRPA1 with HC-030031 had no effect on mechanical sensitivity. These results suggest that the TRPV1 receptor contributes to primary afferent mechanical sensitization and a substantial portion of behavioral mechanical hypersensitivity in SCD mice. Therefore, TRPV1-targeted compounds that lack thermoregulatory side effects may provide relief from pain in patients with SCD.

Vaso-occlusive Painful Events in Sickle Cell Disease: Impact on Child Well-Being

This study describes how painful events affect the health‐related quality of life (HRQL) of children with sickle cell disease (SCD) and determines the responsiveness of a generic HRQL measure in SCD. Our hypotheses were twofold: (1) HRQL is significantly impaired at presentation to the emergency department for a painful event and (2) PedsQL 4.0 Acute Version Generic Core Scales is responsive to change in the evolution of a painful event.

Hydroxyurea in children with sickle cell disease: Practice patterns and barriers to utilization

Hydroxyurea (HU) is underutilized in adults with sickle cell disease (SCD) despite the Multicenter Study of Hydroxyurea (MSH) in sickle cell anemia (1). As little is known about HU utilization in children with SCD we sought to: (1) evaluate patterns of HU utilization; (2) elicit how providers define frequent pain when prescribing HU; and (3) identify barriers to HU use by surveying members of the American Society of Pediatric Hematology/Oncology. Data analysis included descriptive statistics and gamma(2). Of the 350 respondents, 63% care was given for SCD patients. Of these providers, only 9% have 50-90% of patients on HU, while 10% have 30% of patients on HU (35.2% vs. 20%; P = 0.023; gamma(2)). Provider-related barriers to prescribing HU included compliance with: HU (86%), laboratory monitoring (85%), and contraception (85%). Our survey suggests substantial variation in HU utilization in children. Providers accounting for pain managed both in and out of the hospital had more patients on HU. Existing barriers to HU utilization should be addressed to optimize care for children with SCD.

Neuropathic pain in patients with sickle cell disease

Despite the suggestion of a neuropathic component to sickle cell disease (SCD) pain, there are minimal data on the systematic assessment of neuropathic pain in patients with SCD. Neuropathic pain is defined as pain primarily initiated by dysfunction of the peripheral or central nervous system.

Update on the use of hydroxyurea therapy in sickle cell disease

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Postdischarge pain, functional limitations and impact on caregivers of children with sickle cell disease treated for painful events

This study aimed to describe the outcomes of children with sickle cell disease (SCD) after discharge from medical care for vaso‐occlusive painful events and to test the hypothesis that older age, longer length of hospital stay, and a history of frequent vaso‐occlusive painful events will be associated with poor outcomes. Children aged 2–18 years with SCD treated in the emergency department or inpatient unit for a painful event were contacted after discharge to assess: days of pain, days of functional limitations for the child, and days of work/school absenteeism for the caregiver. Descriptive statistics were applied and multivariate logistic regression examined the association between the predictors and outcomes. Fifty‐eight children were enrolled (mean age 10·8 ± 4·8 years, 53·5% female). Postdischarge, 46·5% of children reported three or more days of pain, 54·3% had two or more days of functional limitations, and 24·3% of caregivers missed two or more days of work/school. Children with three or more prior painful events had increased odds of a poor outcome postdischarge (OR 1·79; 95% CI = 1·026, 3·096). In conclusion, acute vaso‐occlusive painful events impact the lives of children with SCD and their caregivers, even after discharge to home.

Hydroxyurea use in sickle cell disease: the battle with low prescription rates, poor patient compliance and fears of toxicities.

Background of sickle cell disease Sickle cell disease (SCD) is the most common inherited blood disorder in the USA, affecting approximately 89,000 Americans or one in 400 African–Americans [1]. SCD is caused by inheritance of the sickle b-globin gene, either in homozygous form (HbSS) or in combination with hemoglobin C (HbSC), b-thalassemia (HbSbthal) or several less common hemoglobin genotypes [2]. This disorder of hemoglobin structure manifests as a chronic debilitating disease characterized by chronic and episodic pain, hemolytic anemia, severe infections, stroke and pulmonary complications beginning in infancy and lasting throughout life [2].

The impact of a multidisciplinary pain management model on sickle cell disease pain hospitalizations

Sickle cell disease (SCD) pain is acute or chronic, leads to school absenteeism, impaired health‐related quality of life and early mortality. Given that little is known about children with SCD and chronic pain, we (1) described characteristics of these children and (2) evaluated the impact of a multidisciplinary pain management model on health care utilization.

Dissatisfaction with hospital care for children with sickle cell disease not due only to race and chronic disease

A previous study reported increased dissatisfaction with hospital care for children with sickle cell disease (SCD); however, its small size excluded determining whether race and chronic disease explained the difference.

Early insights into the neurobiology of pain in sickle cell disease: A systematic review of the literature

Novel insights into the neurobiology of sickle cell disease (SCD) pain have recently been discovered. We systematically reviewed the literature focusing on original research that examined the biology of pain in SCD and/or addressed assessment or treatment of neuropathic pain in SCD. This review of 15 articles that met inclusion criteria provides epidemiological, basic, and clinical data that support central and/or peripheral nervous system abnormalities likely contribute to sickle cell pain. Continued basic and clinical investigation into pain neurobiology is imperative to translate these discoveries into novel ways to assess and treat neuropathic pain and decrease patient suffering. Pediatr Blood Cancer 2015;62:1501–1511.