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Reversal of pathological pain through specific spinal GABAA receptor subtypes

Author

Listed:
  • Julia Knabl

    (Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg)

  • Robert Witschi

    (Institute of Pharmacology and Toxicology, University of Zurich)

  • Katharina Hösl

    (Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg)

  • Heiko Reinold

    (Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg)

  • Ulrike B. Zeilhofer

    (Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg)

  • Seifollah Ahmadi

    (Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg
    Present addresses: Department of Physiology, University of Bonn, D-53111 Bonn, Germany (S.A.); Department of Physiology, University of Münster, D-48149 Münster, Germany (J.B.).)

  • Johannes Brockhaus

    (Institute of Pharmacology and Toxicology, University of Zurich
    Present addresses: Department of Physiology, University of Bonn, D-53111 Bonn, Germany (S.A.); Department of Physiology, University of Münster, D-48149 Münster, Germany (J.B.).)

  • Marina Sergejeva

    (Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg)

  • Andreas Hess

    (Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg)

  • Kay Brune

    (Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg)

  • Jean-Marc Fritschy

    (Institute of Pharmacology and Toxicology, University of Zurich)

  • Uwe Rudolph

    (Institute of Pharmacology and Toxicology, University of Zurich
    Laboratory of Genetic Neuropharmacology, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA)

  • Hanns Möhler

    (Institute of Pharmacology and Toxicology, University of Zurich
    Institute of Pharmaceutical Sciences, ETH Zurich, CH-8093 Zurich, Switzerland
    Collegium Helveticum)

  • Hanns Ulrich Zeilhofer

    (Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg
    Institute of Pharmacology and Toxicology, University of Zurich
    Institute of Pharmaceutical Sciences, ETH Zurich, CH-8093 Zurich, Switzerland)

Abstract

A new target for analgesia The chronic pain that accompanies inflammatory disease and nerve injury is often resistant to conventional analgesics, hence the interest in establishing the mechanisms that induce this pain. Growing evidence points to a loss of synaptic inhibition in the spinal cord as a critical factor in chronic pain. This suggests that a rational therapy should aim at a reversal of this disinhibition. New work using 'knock-in' mice has identified specific GABAA receptor subtypes as keys to this spinal pain. The experimental drug L-838,417, which targets these receptor subtypes, is effective in rat models of inflammatory and neuropathic pain, yet was devoid of sedation, motor impairment and tolerance development expected with less specific GABA agonists.

Suggested Citation

  • Julia Knabl & Robert Witschi & Katharina Hösl & Heiko Reinold & Ulrike B. Zeilhofer & Seifollah Ahmadi & Johannes Brockhaus & Marina Sergejeva & Andreas Hess & Kay Brune & Jean-Marc Fritschy & Uwe Rud, 2008. "Reversal of pathological pain through specific spinal GABAA receptor subtypes," Nature, Nature, vol. 451(7176), pages 330-334, January.
    • Handle: RePEc:nat:nature:v:451:y:2008:i:7176:d:10.1038_nature06493
    DOI: 10.1038/nature06493
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