Endothelin type A receptors mediate pain in a mouse model of sickle cell disease.
Citation: Haematologica. 103(7):1124-1135, 2018 07.PMID: 29545351Institution: MedStar Southern Maryland Hospital CenterDepartment: Intensive Care UnitForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., ExtramuralSubject headings: *Anemia, Sickle Cell/co [Complications] | *Anemia, Sickle Cell/ge [Genetics] | *Pain/et [Etiology] | *Receptor, Endothelin A/ge [Genetics] | Anemia, Sickle Cell/me [Metabolism] | Animals | Biomarkers | Disease Models, Animal | Disease Susceptibility | Endothelin-1/me [Metabolism] | Ganglia, Spinal/cy [Cytology] | Ganglia, Spinal/me [Metabolism] | Ganglia, Spinal/pp [Physiopathology] | Hyperalgesia/di [Diagnosis] | Hyperalgesia/ge [Genetics] | Hyperalgesia/me [Metabolism] | Male | Mice | Mice, Knockout | Mice, Transgenic | Pain/di [Diagnosis] | Pain/me [Metabolism] | Posterior Horn Cells/me [Metabolism] | Receptor, Endothelin A/me [Metabolism]Year: 2018ISSN:- 0390-6078
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Journal Article | MedStar Authors Catalog | Article | 29545351 | Available | 29545351 |
Copyright(c) 2018 Ferrata Storti Foundation.
Sickle cell disease is associated with acute painful episodes and chronic intractable pain. Endothelin-1, a known pain inducer, is elevated in the blood plasma of both sickle cell patients and mouse models of sickle cell disease. We show here that the levels of endothelin-1 and its endothelin type A receptor are increased in the dorsal root ganglia of a mouse model of sickle cell disease. Pharmacologic inhibition or neuron-specific knockdown of endothelin type A receptors in primary sensory neurons of dorsal root ganglia alleviated basal and post-hypoxia evoked pain hypersensitivities in sickle cell mice. Mechanistically, endothelin type A receptors contribute to sickle cell disease-associated pain likely through the activation of NF-kappaB-induced Nav1.8 channel upregulation in primary sensory neurons of sickle cell mice. Our findings suggest that endothelin type A receptor is a potential target for the management of sickle cell disease-associated pain, although this expectation needs to be further verified in clinical settings.
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