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

Academic Article


  • © 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 pos t-h ypoxia evoked pain hype r se nsi tivi ties 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.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Lutz BM; Wu S; Gu X; Atianjoh FE; Li Z; Fox BM; Pollock DM; Tao YX
  • Start Page

  • 1124
  • End Page

  • 1135
  • Volume

  • 103
  • Issue

  • 7