Your browser doesn't support javascript.
loading
Activation of mGluR1 contributes to neuronal hyperexcitability in the rat anterior cingulate cortex via inhibition of HCN channels.
Gao, Shi-Hao; Wen, Hui-Zhong; Shen, Lin-Lin; Zhao, Yan-Dong; Ruan, Huai-Zhen.
Afiliación
  • Gao SH; Department of Neurobiology, College of Basic Medical Science, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
  • Wen HZ; Department of Neurobiology, College of Basic Medical Science, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
  • Shen LL; Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
  • Zhao YD; Department of Neurobiology, College of Basic Medical Science, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
  • Ruan HZ; Department of Neurobiology, College of Basic Medical Science, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China. Electronic address: hzruan163@163.com.
Neuropharmacology ; 105: 361-377, 2016 06.
Article en En | MEDLINE | ID: mdl-26829470
Neuronal hyperexcitability in the anterior cingulate cortex (ACC) is considered as one of the most important pathological changes responsible for the chronification of neuropathic pain. However, the underlying mechanisms remain elusive. In the present study, we investigated the possible mechanisms using a rat model of chronic constriction injury (CCI) to the sciatic nerve. We found a substantial decrease in hyperpolarization-activated/cyclic nucleotide-gated (HCN) currents in layer 5 pyramidal neurons (L5 PNs) in ACC slices, which dramatically increased the excitability of these neurons. This effect could be mimicked in sham slices by activating group 1 metabotropic glutamate receptors, and be blocked in CCI slices by inhibiting metabotropic glutamate receptor subtype 1 (mGluR1). Next, the inhibition of HCN currents was reversed by a protein kinase C (PKC) inhibitor, followed by a reduced neuronal hyperexcitability. Furthermore, HCN channel subtype 1 (HCN1) level was significantly reduced after CCI, whereas mGluR1 level increased. These changes were mainly observed in L5 of the ACC, where HCN1 and mGluR1 were highly colocalized. For behavioral tests, intra-ACC microinjection of mGluR1-shRNA suppressed the CCI-induced behavioral hypersensitivity, particularly thermal hyperalgesia, but not aversive behavior, and this effect was attenuated by the pre-blockade of HCN channels. Taken together, the neuronal hyperexcitability of ACC L5 PNs likely results from an upregulation of mGluR1 and a downstream pathway involving PKC activation and a downregulation of HCN1 in the early phase of neuropathic pain. These alterations may at least in part contribute to the development of behavioral hypersensitivity in CCI rats.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Canales de Potasio / Receptores AMPA / Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización / Giro del Cíngulo / Neuronas Límite: Animals Idioma: En Revista: Neuropharmacology Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Canales de Potasio / Receptores AMPA / Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización / Giro del Cíngulo / Neuronas Límite: Animals Idioma: En Revista: Neuropharmacology Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido