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MicroRNA-96 is required to prevent allodynia by repressing voltage-gated sodium channels in spinal cord.
Sun, Liting; Xia, Ruilong; Jiang, Jinwen; Wen, Ting; Huang, Zhuoya; Qian, Ran; Zhang, Ming-Dong; Zhou, Mingcheng; Peng, Changgeng.
Afiliación
  • Sun L; The First Rehabilitation Hospital of Shanghai, Brain and Spinal Cord Innovation Research Center, School of Medicine, Advanced Institute of Translational Medicine, Tongji University, Shanghai, 200092, China.
  • Xia R; The First Rehabilitation Hospital of Shanghai, Brain and Spinal Cord Innovation Research Center, School of Medicine, Advanced Institute of Translational Medicine, Tongji University, Shanghai, 200092, China.
  • Jiang J; The First Rehabilitation Hospital of Shanghai, Brain and Spinal Cord Innovation Research Center, School of Medicine, Advanced Institute of Translational Medicine, Tongji University, Shanghai, 200092, China.
  • Wen T; The First Rehabilitation Hospital of Shanghai, Brain and Spinal Cord Innovation Research Center, School of Medicine, Advanced Institute of Translational Medicine, Tongji University, Shanghai, 200092, China.
  • Huang Z; The First Rehabilitation Hospital of Shanghai, Brain and Spinal Cord Innovation Research Center, School of Medicine, Advanced Institute of Translational Medicine, Tongji University, Shanghai, 200092, China.
  • Qian R; The First Rehabilitation Hospital of Shanghai, Brain and Spinal Cord Innovation Research Center, School of Medicine, Advanced Institute of Translational Medicine, Tongji University, Shanghai, 200092, China.
  • Zhang MD; Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institutet, Stockholm, 17177, Sweden.
  • Zhou M; The First Rehabilitation Hospital of Shanghai, Brain and Spinal Cord Innovation Research Center, School of Medicine, Advanced Institute of Translational Medicine, Tongji University, Shanghai, 200092, China.
  • Peng C; The First Rehabilitation Hospital of Shanghai, Brain and Spinal Cord Innovation Research Center, School of Medicine, Advanced Institute of Translational Medicine, Tongji University, Shanghai, 200092, China. Electronic address: changgeng.peng@tongji.edu.cn.
Prog Neurobiol ; 202: 102024, 2021 07.
Article en En | MEDLINE | ID: mdl-33636225
Voltage-gated sodium channels (Navs) 1.7, 1.8, and 1.9 are predominately expressed in peripheral sensory neurons and are critical for action potential propagation in nociceptors. Unexpectedly, we found that expression of SCN9A, SCN10A, SCN11A, and SCN2A, the alpha subunit of Nav1.7, Nav1.8, Nav1.9 and Nav1.2, respectively, are up-regulated in spinal dorsal horn (SDH) neurons of miR-96 knockout mice. These mice also have de-repression of CACNA2D1/2 in DRG and display thermal and mechanical allodynia that could be attenuated by intrathecal or intraperitoneal injection of Nav1.7 or Nav1.8 blockers or Gabapentin. Moreover, Gad2::CreERT2 conditional miR-96 knockout mice phenocopied global knockout mice, implicating inhibitory neurons; nerve injury induced significant loss of miR-96 in SDH GABAergic and Glutamatergic neurons in mice which negatively correlated to up-regulation of Nav1.7, Nav1.8, Nav1.9 and Scn2a, this dis-regulation of miR-96 and Navs in SDH neurons contributed to neuropathic pain which can be alleviated by intrathecal injection of Nav1.7 or Nav1.8 blockers. In conclusion, miR-96 is required to avoid allodynia through limiting the expression of VGCCs and Navs in DRG and Navs in SDH in naïve and nerve injury-induced neuropathic pain mice. Our findings suggest that central nervous system penetrating Nav1.7 and Nav1.8 blockers may be efficacious for pain relief.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: MicroARNs / Canales de Sodio Activados por Voltaje / Neuralgia Límite: Animals Idioma: En Revista: Prog Neurobiol Año: 2021 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: MicroARNs / Canales de Sodio Activados por Voltaje / Neuralgia Límite: Animals Idioma: En Revista: Prog Neurobiol Año: 2021 Tipo del documento: Article País de afiliación: China