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Exogenous tumor necrosis factor‐α rapidly alters synaptic and sensory transmission in the adult rat spinal cord dorsal horn
Author(s) -
Youn Dongho,
Wang Haibin,
Jeong SungJin
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21726
Subject(s) - excitatory postsynaptic potential , postsynaptic potential , spinal cord , neuroscience , neurotransmission , hyperalgesia , neuropathic pain , ampa receptor , chemistry , nociception , dorsal root ganglion , inhibitory postsynaptic potential , allodynia , glutamate receptor , receptor , biology , biochemistry
Abstract The proinflammatory cytokine tumor necrosis factor‐α (TNF‐α) is involved in the generation of inflammatory and neuropathic pain. This study investigated if TNF‐α has any effect on spinal synaptic and/or sensory transmission by using whole‐cell recordings of substantia gelatinosa (SG) neurons in transverse lumbar spinal cord slices of adult rats and by using behavioral tests. After intrathecal administration of TNF‐α in adult rats, spontaneous hind paw withdrawal behavior and thermal hyperalgesia were rapidly induced (∼30 min), while mechanical allodynia slowly developed. Bath application of TNF‐α (0.1–1 nM, 8 min) depressed peak amplitude of monosynaptic Aδ and C fiber–evoked excitatory postsynaptic currents (EPSCs) without changing in holding currents and input resistances, whereas this application generally potentiated polysynaptic Aδ fiber‐evoked EPSCs. Moreover, the frequencies, but not the amplitudes, of spontaneous and miniature EPSCs and spontaneous inhibitory postsynaptic currents were significantly increased by bath‐applied TNF‐α in most of the SG neurons. The effects of TNF‐α on Aδ/C fiber–evoked monosynaptic and polysynaptic or spontaneous EPSCs were significantly blocked by 5 μM TNF‐α antagonist that inhibits TNF‐α binding to its type 1 receptor (TNFR1). Because this study also found high protein expression of TNFR1 in the adult dorsal root ganglion and no change of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) induced whole‐cell currents by TNF‐α, we conclude that presynaptic TNFR1 at Aδ/C primary afferent terminals contributes to the rapid alteration of synaptic transmission in the spinal SG, and the development of abnormal pain hypersensitivity by exogenous TNF‐α. © 2008 Wiley‐Liss, Inc.