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Presynaptic NMDARs on spinal nociceptor terminals state-dependently modulate synaptic transmission and pain.
Xie, Rou-Gang; Chu, Wen-Guang; Liu, Da-Lu; Wang, Xu; Ma, Sui-Bin; Wang, Fei; Wang, Fu-Dong; Lin, Zhen; Wu, Wen-Bin; Lu, Na; Liu, Ying-Ying; Han, Wen-Juan; Zhang, Hui; Bai, Zhan-Tao; Hu, San-Jue; Tao, Hui-Ren; Kuner, Thomas; Zhang, Xu; Kuner, Rohini; Wu, Sheng-Xi; Luo, Ceng.
Afiliación
  • Xie RG; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Chu WG; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Liu DL; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Wang X; Department of Radiation Medicine and Protection, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, 710032, Xi'an, China.
  • Ma SB; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Wang F; Research Center for Resource Polypeptide Drugs & College of Life Sciences, Yanan University, 716000, Yanan, China.
  • Wang FD; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Lin Z; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Wu WB; Class 2015, The Fourth Squadron of the Fourth Regiment, School of Basic Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Lu N; Class 2013, The Fourth Squadron of the Second Regiment, School of Basic Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Liu YY; Class 2015, The Fourth Squadron of the Fourth Regiment, School of Basic Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Han WJ; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Zhang H; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Bai ZT; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Hu SJ; Department of Health Statistics, School of Preventive Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Tao HR; Research Center for Resource Polypeptide Drugs & College of Life Sciences, Yanan University, 716000, Yanan, China.
  • Kuner T; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, 710032, Xi'an, China.
  • Zhang X; Department of Spine Surgery, Shenzhen University General Hospital, 518055, Shenzhen, Guangdong, China.
  • Kuner R; Institute for Anatomy and Cell Biology, University of Heidelberg, Im Neuenheimer Feld 307, Heidelberg, 69120, Germany.
  • Wu SX; Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031, Shanghai, China.
  • Luo C; Pharmacology Institute, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg, 69120, Germany.
Nat Commun ; 13(1): 728, 2022 02 07.
Article en En | MEDLINE | ID: mdl-35132099
ABSTRACT
Postsynaptic NMDARs at spinal synapses are required for postsynaptic long-term potentiation and chronic pain. However, how presynaptic NMDARs (PreNMDARs) in spinal nociceptor terminals control presynaptic plasticity and pain hypersensitivity has remained unclear. Here we report that PreNMDARs in spinal nociceptor terminals modulate synaptic transmission in a nociceptive tone-dependent manner. PreNMDARs depresses presynaptic transmission in basal state, while paradoxically causing presynaptic potentiation upon injury. This state-dependent modulation is dependent on Ca2+ influx via PreNMDARs. Small conductance Ca2+-activated K+ (SK) channels are responsible for PreNMDARs-mediated synaptic depression. Rather, tissue inflammation induces PreNMDARs-PKG-I-dependent BDNF secretion from spinal nociceptor terminals, leading to SK channels downregulation, which in turn converts presynaptic depression to potentiation. Our findings shed light on the state-dependent characteristics of PreNMDARs in spinal nociceptor terminals on modulating nociceptive transmission and revealed a mechanism underlying state-dependent transition. Moreover, we identify PreNMDARs in spinal nociceptor terminals as key constituents of activity-dependent pain sensitization.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Nociceptores / Receptores de N-Metil-D-Aspartato / Terminales Presinápticos / Dolor Crónico Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Nociceptores / Receptores de N-Metil-D-Aspartato / Terminales Presinápticos / Dolor Crónico Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: China