title: Different effects of local anesthetics on extracellular signal-regulated kinase phosphorylation in rat dorsal horn neurons.
abstract: Local anesthetics, which are widely known to be neuronal voltage-gated Na(+) channel blockers, also affect a variety of other ion channels, N-methyl-d-asparate (NMDA) receptors and α-amino-3-hydroxy-5-methyl-4-izoxazolepropionic acid (AMPA) receptors. Glutamate, which is released from presynaptic fibers, activates extracellular signal-regulated kinase (ERK) through NMDA and AMPA receptors in spinal dorsal horn neurons. ERK plays a key role in central sensitization, which contributes to the chronicity of pain. We investigated the effects of four representative local anesthetics, lidocaine, tetracaine, levobupivacaine, and ropivacaine on ERK phosphorylation induced by capsaicin, which releases glutamate from presynaptic neurons, NMDA, AMPA, or ionomycin, a calcium ionophore, in dorsal neurons. We observed capsaicin-induced phosphorylation of ERK, which was suppressed by lidocaine, tetracaine, or ropivacaine, but not by levobupivacaine. NMDA-induced phosphorylation of ERK was suppressed by lidocaine, tetracaine, or levobupivacaine, but not by ropivacaine. AMPA-induced phosphorylation of ERK was suppressed by lidocaine or tetracaine, but not by levobupivacaine or ropivacaine. Finally, ionomycin-induced ERK phosphorylation was suppressed by lidocaine, tetracaine, or ropivacaine, but not by levobupivacaine. Our results suggest that local anesthetics contribute to the prevention of the incidence of persistent postsurgical pain with varying intensities and through different mechanisms of action.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan.
authors.forename: Lianxi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tanabe
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan.
authors.forename: Fumi
authors.initials: F
authors.lastname: Yanagidate
authors.affiliation: Department of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan.
authors.forename: Guihua
authors.initials: G
authors.lastname: Chen
authors.affiliation: Muroran City General Hospital, Hokkaido 051-8512, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Dohi
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan. Electronic address: iida@gifu-u.ac.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Iida
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D015759:Ionomycin; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D048049:Extracellular Signal-Regulated MAP Kinases; D002211:Capsaicin
keywords: Extracellular signal-regulated kinase; Levobupivacaine hydrochloride (PubChem CID: 117965); Lidocaine hydrochloride (PubChem CID: 6314); Local anesthetic; Neuron; Postsurgical pain; Ropivacaine hydrochloride (PubChem CID: 175804); Spinal cord; Tetracaine hydrochloride (PubChem CID: 8695)