title: Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: An in vivo patch-clamp analysis.
abstract: Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures in rats. We then performed in vivo patch-clamp recording from spinal substantia gelatinosa (SG) neurons. Intravenous lidocaine had a dose-dependent analgesic effect on the withdrawal response to noxious mechanical stimuli. In the electrophysiological experiments, intravenous lidocaine inhibited the excitatory postsynaptic currents (EPSCs) evoked by noxious pinch stimuli. Intravenous lidocaine also decreased the frequency, but did not change the amplitude, of both spontaneous and miniature EPSCs. However, it did not affect inhibitory postsynaptic currents. Furthermore, intravenous lidocaine induced outward currents in SG neurons. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons. Concomitantly, it hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain.
authors.affiliation: Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi Dori, Chuo-Ku, Niigata City, 951-8510 Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kurabe
authors.affiliation: Department of Information Physiology, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Furue
authors.affiliation: Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi Dori, Chuo-Ku, Niigata City, 951-8510 Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Kohno
mesh_terms: D061605:Administration, Intravenous; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D000700:Analgesics; D018698:Glutamic Acid; D008012:Lidocaine