title: Reactive oxygen species enhance excitatory synaptic transmission in rat spinal dorsal horn neurons by activating TRPA1 and TRPV1 channels.
abstract: Central neuropathic pain (CNP) in the spinal cord, such as chronic pain after spinal cord injury (SCI), is an incurable ailment. However, little is known about the spinal cord mechanisms underlying CNP. Recently, reactive oxygen species (ROS) have been recognized to play an important role in CNP of the spinal cord. However, it is unclear how ROS affect synaptic transmission in the dorsal horn of the spinal cord. To clarify how ROS impact on synaptic transmission, we investigated the effects of ROS on synaptic transmission in rat spinal cord substantia gelatinosa (SG) neurons using whole-cell patch-clamp recordings. Administration of tert-butyl hydroperoxide (t-BOOH), an ROS donor, into the spinal cord markedly increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in SG neurons. This t-BOOH-induced enhancement was not suppressed by the Na(+) channel blocker tetrodotoxin. However, in the presence of a non-N-methyl-D-aspartate glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, t-BOOH did not generate any sEPSCs. Furthermore, in the presence of a transient receptor potential ankyrin 1 (TRPA1) channel antagonist (HC-030031) or a transient receptor potential vanilloid 1 (TRPV1) channel antagonist (capsazepine or AMG9810), the t-BOOH-induced increase in the frequency of sEPSCs was inhibited. These results indicate that ROS enhance the spontaneous release of glutamate from presynaptic terminals onto SG neurons through TRPA1 and TRPV1 channel activation. Excessive activation of these ion channels by ROS may induce central sensitization in the spinal cord and result in chronic pain such as that following SCI.
authors.affiliation: Pain Research Center, Kansai University of Health Sciences, Kumatori, Osaka 590-0482, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nishio
authors.forename: W
authors.initials: W
authors.lastname: Taniguchi
authors.forename: Y K
authors.initials: YK
authors.lastname: Sugimura
authors.forename: N
authors.initials: N
authors.lastname: Takiguchi
authors.forename: M
authors.initials: M
authors.lastname: Yamanaka
authors.forename: Yasukuni
authors.initials: Y
authors.lastname: Kiyoyuki
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.forename: N
authors.initials: N
authors.lastname: Miyazaki
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Nakatsuka
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D008297:Male; D009924:Organ Culture Techniques; D020671:Posterior Horn Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C493922:Trpv1 protein, rat
keywords: 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl; 6-cyano-7-nitroquinoxaline-2,3-dione; AITC; AMPA; CNP; CNQX; DRG; EPSC; IPSC; LTP; N-acetylcysteine; N-methyl-d-aspartate; NAC; NMDA; PBN; RNS; ROS; SCI; SG; TEMPOL; TRP; TRPA1; TRPV1; TTX; allyl isothiocyanate; central neuropathic pain; dorsal root ganglion; excitatory postsynaptic currents; inhibitory postsynaptic currents; long-term potentiation; mEPSCs; miniature EPSCs; pain; phenyl-N-tert-butylnitrone; reactive nitrogen species; reactive oxygen species; sEPSC; spinal cord; spinal cord injury; spontaneous excitatory postsynaptic currents; substantia gelatinosa; t-BOOH; tert-butyl hydroperoxide; tetrodotoxin; transient receptor potential; transient receptor potential ankyrin 1; transient receptor potential vanilloid 1; α-amino-3-hydroxy-5-methyl-4-isozazole propionate