title: Phosphorylation of NR2B NMDA subunits by protein kinase C in arcuate nucleus contributes to inflammatory pain in rats.
abstract: The arcuate nucleus (ARC) of the hypothalamus plays a key role in pain processing. Although it is well known that inhibition of NMDA receptor (NMDAR) in ARC attenuates hyperalgesia induced by peripheral inflammation, the underlying mechanism of NMDAR activation in ARC remains unclear. Protein kinase C (PKC) is involved in several signalling cascades activated in physiological and pathological conditions. Therefore, we hypothesised that upregulation of PKC activates NMDARs in the ARC, thus contributing to inflammatory hyperalgesia. Intra-ARC injection of chelerythrine (CC), a specific PKC inhibitor, attenuated complete Freund's adjuvant (CFA) induced thermal and mechanical hyperalgesia in a dose-dependent manner. In vivo extracellular recordings showed that microelectrophoresis of CC or MK-801 (a NMDAR antagonist) significantly reduced the enhancement of spontaneous discharges and pain-evoked discharges of ARC neurons. In addition, CFA injection greatly enhanced the expression of total and phosphorylated PKCγ in the ARC. Interestingly, CFA injection also remarkably elevated the level of phosphorylated NR2B (Tyr1472) without affecting the expression of total NR2B. Importantly, intra-ARC injection of CC reversed the upregulation of phosphorylated NR2B subunits in the ARC. Taken together, peripheral inflammation leads to an activation of NMDARs mediated by PKC activation in the ARC, thus producing thermal and mechanical hyperalgesia.
authors.affiliation: Key Laboratory of Pain Basic Research and Clinical Therapy, Department of Physiology &Neurobiology, Medical College of Soochow University, Suzhou 215123, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Bu
authors.affiliation: Key Laboratory of Pain Basic Research and Clinical Therapy, Department of Physiology &Neurobiology, Medical College of Soochow University, Suzhou 215123, P.R. China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Tian
authors.affiliation: Key Laboratory of Pain Basic Research and Clinical Therapy, Department of Physiology &Neurobiology, Medical College of Soochow University, Suzhou 215123, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Gong
authors.affiliation: Key Laboratory of Pain Basic Research and Clinical Therapy, Department of Physiology &Neurobiology, Medical College of Soochow University, Suzhou 215123, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Pain Basic Research and Clinical Therapy, Department of Physiology &Neurobiology, Medical College of Soochow University, Suzhou 215123, P.R. China.|Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou 215123, P.R. China.
authors.forename: Guang-Yin
authors.initials: GY
authors.lastname: Xu
authors.affiliation: Key Laboratory of Pain Basic Research and Clinical Therapy, Department of Physiology &Neurobiology, Medical College of Soochow University, Suzhou 215123, P.R. China.|Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou 215123, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Tao
authors.affiliation: Key Laboratory of Pain Basic Research and Clinical Therapy, Department of Physiology &Neurobiology, Medical College of Soochow University, Suzhou 215123, P.R. China.|Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou 215123, P.R. China.
authors.forename: Xinghong
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism* / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D053119:Benzophenanthridines / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005620:Freund's Adjuvant / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D053119:Benzophenanthridines; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D005620:Freund's Adjuvant; C016299:chelerythrine; D011493:Protein Kinase C