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ANESTHETIC PHARMACOLOGY

Xenon Blocks the Induction of Synaptic Long-Term Potentiation in Pain Pathways in the Rat Spinal Cord In Vivo

Justus Benrath, MD^*, Christina Kempf, PhD, Michael Georgieff, MD, PhD, and Jürgen Sandkühler, MD, PhD

From the *Klinische Abteilung für Anästhesie und Allgemeine Intensivmedizin B, Medizinische Universität Wien, Währinger Gürtel 18-20, AKH, A-1090 Wien, Austria; Institut für Physiologie und Pathophysiologie, Universität Heidelberg, Im Neuenheimer Feld 326, D-69120 Heidelberg; Klinik für Anästhesiologie, Universitätsklinikum Ulm, Steinhövelstrasse 9, D-89075 Ulm, Germany; and Zentrum für Hirnforschung, Abteilung für Neurophysiologie, Medizinische Universität Wien, Spitalgasse 4, A-1090 Wien, Austria.

BACKGROUND: Xenon’s (Xe) mechanisms for producing anesthesia and analgesia are not fully understood. We tested the effect of Xe equilibrated in a lipid formulation or normal saline on spinal C-fiber-evoked potentials and on the induction of synaptic long-term potentiation (LTP).

METHODS: C-fiber-evoked field potentials were recorded in the superficial lumbar spinal cord in response to supramaximal electrical stimulation of the sciatic nerve. Anesthesia was maintained with isoflurane in one-third O₂ and two-thirds N₂O. Xe equilibrated at a concentration of 600 µL/mL of Lipofundin MCT® 20%, (n = 5) or solvent alone (n = 3), and Xe equilibrated at a concentration of 100 µL/mL of normal saline (n = 7) or saline alone (n = 7) was given IV under apnea. High-frequency stimulation of the sciatic nerve was applied 60 min after the injection of Xe-containing formulations or solvents [to induce LTP].

RESULTS: High-frequency stimulation potentiated C-fiber-evoked potentials to 156% ± 14% (mean ± sem) of control. Low-dose Xe in saline 0.9% blocked the induction of LTP. High-dose Xe equilibrated in MC® 20% showed no additional effect when compared with the solvent, which blocked the induction of LTP.

CONCLUSION: Low-dose Xe in saline 0.9% revealed no antinociceptive, but preventive, action in spinal pain pathways.

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