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Central sensitization associated with low fetal hemoglobin levels in adults with sickle cell anemia.

ABSTRACT: BACKGROUND AND AIMS:Pain is the hallmark of sickle cell anemia (SCA), presenting as recurrent acute events or chronic pain. Central sensitization, or enhanced excitability of the central nervous system, alters pain processing and contributes to the maintenance of chronic pain. Individuals with SCA demonstrate enhanced sensitivity to painful stimuli however central mechanisms of pain have not been fully explored. We hypothesized that adults with SCA would show evidence of central sensitization as observed in other diseases of chronic pain. METHODS:We conducted a prospective study of static and dynamic quantitative sensory tests in 30 adults with SCA and 30 matched controls. RESULTS:Static thermal testing using cold stimuli showed lower pain thresholds (p=0.04) and tolerance (p=0.04) in sickle cell subjects, but not for heat. However, SCA subjects reported higher pain ratings with random heat pulses (p<0.0001) and change in scores with temporal summation at the heat pain threshold (p=0.002). Similarly, with the use of pressure pain stimuli, sickle cell subjects reported higher pain ratings (p=0.04), but not higher pressure pain tolerance/thresholds or allodynia to light tactile stimuli. Temporal summation pain score changes using 2 pinprick probes (256 and 512mN) were significantly greater (p=0.004 and p=0.008) with sickle cell, and delayed recovery was associated with lower fetal hemoglobin (p=0.002 and 0.003). CONCLUSIONS:Exaggerated temporal summation responses provide evidence of central sensitization in SCA. IMPLICATIONS:The association with fetal hemoglobin suggests this known SCA modifier may have a therapeutic role in modulating central sensitization.

SUBMITTER: Darbari DS

PROVIDER: S-EPMC5726893 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Central sensitization associated with low fetal hemoglobin levels in adults with sickle cell anemia.

Darbari Deepika S DS Vaughan Kathleen J KJ Roskom Katherine K Seamon Cassie C Diaw Lena L Quinn Meghan M Conrey Anna A Schechter Alan N AN Haythornthwaite Jennifer A JA Waclawiw Myron A MA Wallen Gwenyth R GR Belfer Inna I Taylor James G JG

Scandinavian journal of pain 20170930

<h4>Background and aims</h4>Pain is the hallmark of sickle cell anemia (SCA), presenting as recurrent acute events or chronic pain. Central sensitization, or enhanced excitability of the central nervous system, alters pain processing and contributes to the maintenance of chronic pain. Individuals with SCA demonstrate enhanced sensitivity to painful stimuli however central mechanisms of pain have not been fully explored. We hypothesized that adults with SCA would show evidence of central sensitiz ...[more]

PMID: 28969994

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Project description:BACKGROUND:Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea. OBJECTIVES:We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010. METHODS:An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648. RESULTS:Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003-1.006, p<0.0.0001), kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00-1.27, p = 0.043), and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23-4.02, p = 0.0082). Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34-0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15-35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17-0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels. CONCLUSIONS:Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose, ideally before organ damage occurs. Prospective studies are indicated to validate these findings.

Dataset Information

Central sensitization associated with low fetal hemoglobin levels in adults with sickle cell anemia.

Publications

Central sensitization associated with low fetal hemoglobin levels in adults with sickle cell anemia.

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