Cdyl Deficiency Brakes Neuronal Excitability and Nociception through Promoting Kcnb1 Transcription in Peripheral Sensory Neurons.
Adv Sci (Weinh)
; 9(10): e2104317, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35119221
ABSTRACT
Epigenetic modifications are involved in the onset, development, and maintenance of pain; however, the precise epigenetic mechanism underlying pain regulation remains elusive. Here it is reported that the epigenetic factor chromodomain Y-like (CDYL) is crucial for pain processing. Selective knockout of CDYL in sensory neurons results in decreased neuronal excitability and nociception. Moreover, CDYL facilitates histone 3 lysine 27 trimethylation (H3K27me3) deposition at the Kcnb1 intron region thus silencing voltage-gated potassium channel (Kv ) subfamily member Kv 2.1 transcription. Loss function of CDYL enhances total Kv and Kv 2.1 current density in dorsal root ganglia and knockdown of Kv 2.1 reverses the pain-related phenotypes of Cdyl deficiency mice. Furthermore, focal administration of a novel potent CDYL antagonist blunts nociception and attenuates neuropathic pain. These findings reveal that CDYL is a critical regulator of pain sensation and shed light on the development of novel analgesics targeting epigenetic mechanisms.
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Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio Shab
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Proteínas Correpressoras
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Nociceptividade
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Hidroliases
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article