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B.M. Lutz et al.
other transcription factors or molecules in ET-1/ETA receptor-mediated Nav1.8 upregulation in HbSS DRG could not be excluded.
In conclusion, this study provides evidence for one pos-
ETA receptor antagonists have been used in phase II/III clinical trials for cancer treatment18,19 and are beneficial for SCD-related pulmonary hypertension,16 targeting DRG ETA receptors may have potential therapeutic value for SCD-associated pain management.
Funding
This work was supported by NIH grants (R01NS094664, R01NS094224, R01DA033390, and U01HL117684) to YXT and by a NIH research Fellowship (F31NS092310) to BML at Rutgers New Jersey Medical School. We thank Dr. Roger Howell at Rutgers New Jersey Medical School for his assistance with animal radiation.
sible mechanism by which ET-1/ET receptors contribute A
to SCD-associated pain likely through the NF-κB-trig- gered upregulation of Nav1.8 in primary sensory neurons. We identified the ability of ABT-627, an ETA receptor- specific antagonist,24 to alleviate basal and post-hypoxia evoked pain hypersensitivity in SCD mice. At the dosages used, ABT-627 produced pain relief that persisted for the entire testing period (at least 7 hours) with no noticeable side effects. Given that ABT-627 and similar
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