期刊
HAEMATOLOGICA
卷 103, 期 7, 页码 1124-1135出版社
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2017.187013
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资金
- NIH [R01NS094664, R01NS094224, R01DA033390, U01HL117684]
- NIH research Fellowship at Rutgers New Jersey Medical School [F31NS092310]
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-kappa 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.
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