Peripheral NMDA Receptors Mediate Antidromic Nerve Stimulation-Induced Tactile Hypersensitivity in the Rat.

Jun Ho Jang,Dong-Wook Kim,Se Jung Jung,Taick Sang Nam,Joong Woo Leem,Jaebeom Jun

doi:10.1155/2015/793624

Jun Ho Jang, Dong-Wook Kim + Show 4 more

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https://doi.org/10.1155/2015/793624

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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.

Highlights

Primary afferent nociceptors are responsible for converting harmful stimuli in the peripheral tissue into internal electrical impulses and conveying these impulses to the central nervous system for pain perception
We investigated using rats with L5 dorsal root rhizotomy (DR) whether a high-level tetanic electrical stimulation (ES) (2–4 mA, 0.5 ms pulse, 4 Hz, and 5 min) of the L5 spinal nerve (L5 SN) (L5 SN-ES) induced tactile hypersensitivity on the L4 dermatome
The tactile sensitivity was tested by measuring paw withdrawal threshold (PWT) using von Frey filaments applied to the center of the hind-paw glabrous skin surrounded by the tori, which is almost matched to the midpoint of the L4 plantar dermatome (Figure 1)

Summary

Introduction

Primary afferent nociceptors are responsible for converting harmful stimuli in the peripheral tissue into internal electrical impulses and conveying these impulses to the central nervous system for pain perception. In addition to their afferent functions, evidence indicates that nociceptors have local efferent functions. There is significant evidence for the modulatory role of Glu in peripheral nociception Both ionotropic and metabotropic Glu receptors (mGluRs) are present in the peripheral terminals of unmyelinated afferents [9,10,11,12,13]. Peripheral Glu is able to increase the excitability of nociceptors under both normal

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