Endothelin type A receptors mediate pain in a mouse model of sickle cell disease.
Endothelin type A receptors mediate pain in a mouse model of sickle cell disease.
- 2018
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.
English
0390-6078
10.3324/haematol.2017.187013 [doi] haematol.2017.187013 [pii] PMC6029538 [pmc]
*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]
MedStar Southern Maryland Hospital Center
Intensive Care Unit
Journal Article
Research Support, N.I.H., Extramural
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.
English
0390-6078
10.3324/haematol.2017.187013 [doi] haematol.2017.187013 [pii] PMC6029538 [pmc]
*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]
MedStar Southern Maryland Hospital Center
Intensive Care Unit
Journal Article
Research Support, N.I.H., Extramural