title: Xenon inhibits excitatory but not inhibitory transmission in rat spinal cord dorsal horn neurons.
abstract: BACKGROUND
  The molecular targets for the promising gaseous anaesthetic xenon are still under investigation. Most studies identify N-methyl-D-aspartate (NMDA) receptors as the primary molecular target for xenon, but the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptors is less clear. In this study we evaluated the effect of xenon on excitatory and inhibitory synaptic transmission in the superficial dorsal horn of the spinal cord using in vitro patch-clamp recordings from rat spinal cord slices. We further evaluated the effects of xenon on innocuous and noxious stimuli using in vivo patch-clamp method.
  
  
  RESULTS
  In vitro, xenon decreased the amplitude and area under the curve of currents induced by exogenous NMDA and AMPA and inhibited dorsal root stimulation-evoked excitatory postsynaptic currents. Xenon decreased the amplitude, but not the frequency, of miniature excitatory postsynaptic currents. There was no discernible effect on miniature or evoked inhibitory postsynaptic currents or on the current induced by inhibitory neurotransmitters. In vivo, xenon inhibited responses to tactile and painful stimuli even in the presence of NMDA receptor antagonist.
  
  
  CONCLUSIONS
  Xenon inhibits glutamatergic excitatory transmission in the superficial dorsal horn via a postsynaptic mechanism. There is no substantial effect on inhibitory synaptic transmission at the concentration we used. The blunting of excitation in the dorsal horn lamina II neurons could underlie the analgesic effect of xenon.
authors.affiliation: Division of Anaesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi, Chuo ku, Niigata 951-8510, Japan. stefgeo@med.niigata-u.ac.jp
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Georgiev
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Furue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Baba
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Kohno
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000166:cytology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D014978:Xenon / Q000494:pharmacology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D014978:Xenon; D013779:Tetrodotoxin; D016202:N-Methylaspartate; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine
references.citation: Anesthesiology. 2009 Dec;111(6):1297-307
references.pmid: 19934875
references.citation: Neuroimage. 2010 Jan 1;49(1):720-30
references.pmid: 19703572
references.citation: Anesth Analg. 2007 Jan;104(1):106-11
references.pmid: 17179253
references.citation: Semin Cell Dev Biol. 2006 Oct;17(5):592-604
references.pmid: 17110139
references.citation: Anesth Analg. 2000 Dec;91(6):1542-9
references.pmid: 11094015
references.citation: Br J Anaesth. 1995 Jun;74(6):670-3
references.pmid: 7640122
references.citation: Best Pract Res Clin Anaesthesiol. 2005 Sep;19(3):365-79
references.pmid: 16013687
references.citation: Anesthesiology. 2000 Feb;92(2):507-15
references.pmid: 10691239
references.citation: Anesthesiology. 2008 Dec;109(6):998-1006
references.pmid: 19034096
references.citation: Pain. 2004 Jun;109(3):210-213
references.pmid: 15157680
references.citation: Basic Clin Pharmacol Toxicol. 2008 Jul;103(1):31-5
references.pmid: 18598297
references.citation: Eur J Pharmacol. 2004 Aug 2;496(1-3):71-6
references.pmid: 15288577
references.citation: Anesthesiology. 2005 Sep;103(3):508-13
references.pmid: 16129975
references.citation: J Physiol. 1999 Dec 1;521 Pt 2:529-35
references.pmid: 10581321
references.citation: Anesth Analg. 2002 Feb;94(2):313-8, table of contents
references.pmid: 11812690
references.citation: FASEB J. 2008 Apr;22(4):1275-86
references.pmid: 18024836
references.citation: Anesth Analg. 2008 Jan;106(1):129-34, table of contents
references.pmid: 18165567
references.citation: Pain. 2008 Jan;134(1-2):24-31
references.pmid: 17481820
references.citation: Prog Neurobiol. 1999 Jan;57(1):1-164
references.pmid: 9987804
references.citation: Br J Anaesth. 2005 Apr;94(4):479-85
references.pmid: 15695547
references.citation: Anesth Analg. 1998 Aug;87(2):419-24
references.pmid: 9706943
references.citation: J Cereb Blood Flow Metab. 2003 Oct;23(10):1168-73
references.pmid: 14526227
references.citation: Anesth Analg. 2004 Jun;98(6):1718-1723
references.pmid: 15155334
references.citation: Eur J Neurosci. 2009 Feb;29(3):518-28
references.pmid: 19222560
references.citation: Br J Anaesth. 1998 Nov;81(5):742-7
references.pmid: 10193287
references.citation: J Neurosci. 1992 Aug;12(8):3025-41
references.pmid: 1353793
references.citation: Br J Anaesth. 2002 Nov;89(5):739-46
references.pmid: 12393773
references.citation: Anesthesiology. 2002 Jun;96(6):1485-91
references.pmid: 12170064
references.citation: Anesth Analg. 1999 Apr;88(4):893-7
references.pmid: 10195543
references.citation: Eur J Pain. 2010 Jan;14(1):17-22
references.pmid: 19261495
references.citation: Anesthesiology. 2006 Jul;105(1):187-97
references.pmid: 16810011
references.citation: Anesthesiology. 2007 Nov;107(5):756-67
references.pmid: 18073551
references.citation: Nature. 1998 Nov 26;396(6709):324
references.pmid: 9845069
references.citation: J Neurosci. 2004 Jun 23;24(25):5766-77
references.pmid: 15215299
references.citation: Anesthesiology. 2004 Feb;100(2):347-58
references.pmid: 14739810
references.citation: Anesth Analg. 1997 Jun;84(6):1372-6
references.pmid: 9174323
references.citation: Anesthesiology. 2000 Oct;93(4):1095-101
references.pmid: 11020766
references.citation: Anesthesiology. 1998 Sep;89(3):715-22
references.pmid: 9743410
references.citation: Anesthesiology. 2000 Apr;92(4):1055-66
references.pmid: 10754626
references.citation: Minerva Anestesiol. 2009 Jan-Feb;75(1-2):37-45
references.pmid: 18475253