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Endothelin type A receptors mediate pain in a mouse model of sickle cell disease.


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-?B-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.

SUBMITTER: Lutz BM 

PROVIDER: S-EPMC6029538 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Endothelin type A receptors mediate pain in a mouse model of sickle cell disease.

Lutz Brianna Marie BM   Wu Shaogen S   Gu Xiyao X   Atianjoh Fidelis E FE   Li Zhen Z   Fox Brandon M BM   Pollock David M DM   Tao Yuan-Xiang YX  

Haematologica 20180315 7


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 neur  ...[more]

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