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: Jun Ho Jang, Taick Sang Nam, Jaebeom Jun, Se Jung Jung, Dong-Wook Kim, Joong Woo Leem
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2015 Pg. 793624 ( 2015) ISSN: 1466-1861 [Electronic] United States
• PMID: 26770021 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoquinolines
• Quinoxalines
• Receptors, N-Methyl-D-Aspartate
• Sulfonamides
• 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
• Glutamic Acid
• Dizocilpine Maleate
• Cyclic AMP-Dependent Protein Kinases
• Protein Kinase C
• N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide

Topics

• Animals
• Cyclic AMP-Dependent Protein Kinases (physiology)
• Dizocilpine Maleate (pharmacology)
• Electric Stimulation
• Glutamic Acid (physiology)
• Hyperalgesia (etiology)
• Isoquinolines (pharmacology)
• Male
• Protein Kinase C (physiology)
• Quinoxalines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, N-Methyl-D-Aspartate (physiology)
• Sulfonamides (pharmacology)
• Tibial Nerve (physiology)