Selective inhibition of CaV3.2 channels reverses hyperexcitability of peripheral nociceptors and alleviates postsurgical pain.
Sci Signal
; 11(545)2018 08 28.
Article
en En
| MEDLINE
| ID: mdl-30154101
ABSTRACT
Pain-sensing sensory neurons of the dorsal root ganglion (DRG) can become sensitized or hyperexcitable in response to surgically induced peripheral tissue injury. We investigated the potential role and molecular mechanisms of nociceptive ion channel dysregulation in acute pain conditions such as those resulting from skin and soft tissue incision. We used selective pharmacology, electrophysiology, and mouse genetics to link increased current densities arising from the CaV3.2 isoform of T-type calcium channels (T-channels) to nociceptive sensitization using a clinically relevant rodent model of skin and deep tissue incision. Furthermore, knockdown of the CaV3.2-targeting deubiquitinating enzyme USP5 or disruption of USP5 binding to CaV3.2 channels in peripheral nociceptors resulted in a robust antihyperalgesic effect in vivo and substantial T-current reduction in vitro. Our study provides mechanistic insight into the role of plasticity in CaV3.2 channel activity after surgical incision and identifies potential targets for perioperative pain that may greatly decrease the need for narcotics and potential for drug abuse.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dolor
/
Complicaciones Posoperatorias
/
Nociceptores
/
Canales de Calcio Tipo T
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Sci Signal
Asunto de la revista:
CIENCIA
/
FISIOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos