This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Haseneder, R. Articles by Hapfelmeier, G. Search for Related Content PubMed PubMed Citation Articles by Haseneder, R. Articles by Hapfelmeier, G. Related Collections Mechanisms Pharmacology

---

ANESTHETIC PHARMACOLOGY

Isoflurane Reduces Glutamatergic Transmission in Neurons in the Spinal Cord Superficial Dorsal Horn: Evidence for a Presynaptic Site of an Analgesic Action

Rainer Haseneder^*, Jörge Kurz^*, Hans-Ulrich U. Dodt, Eberhard Kochs^*, Walter Zieglgänsberger, Michaela Scheller^*, Gerhard Rammes, and Gerhard Hapfelmeier^*

*Department of Anaesthesiology, Klinikum rechts der Isar, Technische Universität München, and the Department of Clinical Neuropharmacology, Max-Planck-Institute of Psychiatry, Munich, Germany

Address correspondence and reprint requests to Rainer Haseneder, Max-Planck-Institute of Psychiatry, Munich, Kraepelinstrasse 2-10, 80804 Munich, Germany. Address email to haseneder{at}mpipsykl mpg.de.

The minimum alveolar concentration (MAC) of a volatile anesthetic defines anesthetic potency in terms of a suppressed motor response to a noxious stimulus. Therefore, the MAC of an anesthetic might in part reflect depression of motor neuron excitability. In the present study we evaluated the effect of isoflurane (ISO) on neurons in the substantia gelatinosa driven synaptically by putative nociceptive inputs in an in vitro spinal cord preparation of the rat. Whole-cell patch-clamp recordings were performed in neurons with their soma in the substantia gelatinosa of transverse rat spinal cord slices. We investigated the effect of ISO on excitatory postsynaptic currents (EPSC) evoked by dorsal root stimulation (eEPSC), spontaneous (sEPSC), and miniature (mEPSC) EPSC. ISO reversibly reduced the amplitude of eEPSC to 39% ± 22% versus control. ISO decreased the frequency of sEPSC and mEPSC to 39% ± 26% and 63% ± 7%. Neither the amplitudes nor the kinetics of mEPSC and sEPSC were altered by ISO. We conclude that ISO depresses glutamatergic synaptic transmission of putative nociceptive primary-afferent inputs, presumably by reducing the release of the excitatory transmitter. This effect may contribute to an antinociceptive action of volatile anesthetics at the spinal cord level.

IMPLICATIONS: The present electrophysiological in vitro experiments provide evidence that the volatile anesthetic isoflurane reduces excitatory transmitter release at the first site of synaptic integration of nociceptive inputs, the spinal cord superficial dorsal horn. This effect may contribute to the anesthetic action of volatile anesthetics at the spinal cord level.

This article has been cited by other articles:

				P. B. Schwarz, N. Yee, S. Mir, and J. H. Peever Noradrenaline triggers muscle tone by amplifying glutamate-driven excitation of somatic motoneurones in anaesthetized rats J. Physiol., December 1, 2008; 586(23): 5787 - 5802. [Abstract] [Full Text] [PDF]

				J. Kim, A. Yao, R. Atherley, E. Carstens, S. L. Jinks, and J. F. Antognini Neurons in the Ventral Spinal Cord Are More Depressed by Isoflurane, Halothane, and Propofol Than Are Neurons in the Dorsal Spinal Cord Anesth. Analg., October 1, 2007; 105(4): 1020 - 1026. [Abstract] [Full Text] [PDF]

				G. A. Mashour Integrating the Science of Consciousness and Anesthesia Anesth. Analg., October 1, 2006; 103(4): 975 - 982. [Abstract] [Full Text] [PDF]

				R. I. Westphalen and H. C. Hemmings Jr. Volatile Anesthetic Effects on Glutamate versus GABA Release from Isolated Rat Cortical Nerve Terminals: Basal Release J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 208 - 215. [Abstract] [Full Text] [PDF]