Endothelin type A receptors mediate pain in a mouse model of sickle cell disease
EHA Library. Lutz B. Jul 1, 2018; 224104 Topic: 1Ae Thalassemia including HbE disorders
Brianna Marie Lutz
Brianna Marie Lutz
Contributions
Journal Abstract

Co-Authors: Shaogen Wu, Xiyao Gu, Fidelis E. Atianjoh, Zhen Li, Brandon M. Fox, David M. Pollock, Yuan-Xiang Tao

Abstract: 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-κB-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.

Article Number: 1124

Doi: 10.3324/haematol.2017.187013

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