title: Peripheral NMDA Receptors Mediate Antidromic Nerve Stimulation-Induced Tactile Hypersensitivity in the Rat.
abstract: We investigated the role of peripheral NMDA receptors (NMDARs) in antidromic nerve stimulation-induced tactile hypersensitivity outside the skin area innervated by stimulated nerve. Tetanic electrical stimulation (ES) of the decentralized L5 spinal nerve, which induced enlargement of plasma extravasation, resulted in tactile hypersensitivity in the L4 plantar dermatome of the hind-paw. When intraplantar (i.pl.) injection was administered into the L4 dermatome before ES, NMDAR and group-I metabotropic Glu receptor (mGluR) antagonists and group-II mGluR agonist but not AMPA/kainate receptor antagonist prevented ES-induced hypersensitivity. I.pl. injection of PKA or PKC inhibitors also prevented ES-induced hypersensitivity. When the same injections were administered after establishment of ES-induced hypersensitivity, hypersensitivity was partially reduced by NMDAR antagonist only. In naïve animals, i.pl. Glu injection into the L4 dermatome induced tactile hypersensitivity, which was blocked by NMDAR antagonist and PKA and PKC inhibitors. These results suggest that the peripheral release of Glu, induced by antidromic nerve stimulation, leads to the expansion of tactile hypersensitive skin probably via nociceptor sensitization spread due to the diffusion of Glu into the skin near the release site. In addition, intracellular PKA- and PKC-dependent mechanisms mediated mainly by NMDAR activation are involved in Glu-induced nociceptor sensitization and subsequent hypersensitivity.
authors.affiliation: Dental Research Institute, Seoul National University, Seoul 110-744, Republic of Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Taick Sang
authors.initials: TS
authors.lastname: Nam
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Jaebeom
authors.initials: J
authors.lastname: Jun
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Se Jung
authors.initials: SJ
authors.lastname: Jung
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Graduate Program in Cognitive Science Yonsei University, Seoul 120-752, Republic of Korea.
authors.forename: Joong Woo
authors.initials: JW
authors.lastname: Leem
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000502:physiology; D006930:Hyperalgesia / Q000209:etiology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D011493:Protein Kinase C / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013979:Tibial Nerve / Q000502:physiology*
chemical_list: D007546:Isoquinolines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D013449:Sulfonamides; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide