Nociceptors protect sickle cell disease mice from vaso-occlusive episodes and chronic organ damage.
J Exp Med
; 218(1)2021 01 04.
Article
em En
| MEDLINE
| ID: mdl-33045060
ABSTRACT
Sickle cell disease (SCD) is a common hereditary hematologic disorder. SCD patients suffer from acute vaso-occlusive episodes (VOEs), chronic organ damage, and premature death, with few therapeutic options. Although severe pain is a major clinical manifestation of SCD, it remains unknown whether nociception plays a role in SCD pathogenesis. To address this question, we generated nociceptor-deficient SCD mice and found, unexpectedly, that the absence of nociception led to more severe and more lethal VOE, indicating that somatosensory nerves protect SCD mice from VOE. Mechanistically, the beneficial effects of sensory nerves were induced by the neuropeptide calcitonin gene-related peptide (CGRP), which acted on hematopoietic cells. Additionally, oral capsaicin consumption, which can activate somatosensory nerves by binding to TRPV1, dramatically alleviated acute VOE and significantly prevented chronic liver and kidney damage in SCD mice. Thus, the manipulation of nociception may provide a promising approach to treat SCD.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células Receptoras Sensoriais
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Doenças Vasculares
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Nociceptores
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Capsaicina
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Anemia Falciforme
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article