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PGE2 selectively blocks inhibitory glycinergic neurotransmission onto rat superficial dorsal horn neurons

Nature Neuroscience volume 5, pages 3440 (2002) | Download Citation

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Abstract

Despite the crucial role that prostaglandins (PGs) have in the sensitization of the central nervous system to pain, their cellular and molecular targets leading to increased pain perception have remained elusive. Here we investigated the effects of PGE2 on fast synaptic transmission onto neurons in the rat spinal cord dorsal horn, the first site of synaptic integration in the pain pathway. We identified the inhibitory (strychnine-sensitive) glycine receptor as a specific target of PGE2. PGE2, but not PGF, PGD2 or PGI2, reduced inhibitory glycinergic synaptic transmission in low nanomolar concentrations, whereas GABAA, AMPA and NMDA receptor-mediated transmission remained unaffected. Inhibition of glycine receptors occurred via a postsynaptic mechanism involving the activation of EP2 receptors, cholera-toxin-sensitive G-proteins and cAMP-dependent protein kinase. Via this mechanism, PGE2 may facilitate the transmission of nociceptive input through the spinal cord dorsal horn to higher brain areas where pain becomes conscious.

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Acknowledgements

This work was supported in part by grants from the Deutsche Forschungsgemeinschaft (SFB 353/A8 to H.U.Z. and SFB/B15 to W.L.N.) and a stipend from the Graduiertenkolleg GRK 22 to S.L. The authors thank C.-M. Becker, K. Brune and P.W. Reeh for critically reading the manuscript and S. Gabriel, K. Löschner and H. Symowski for technical assistance.

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Author notes

    • Seifollah Ahmadi
    •  & Sebastian Lippross

    The first two authors contributed equally to this work

Affiliations

  1. Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Emil-Fischer-Zentrum, Fahrstrasse 17, D-91054 Erlangen, Germany

    • Seifollah Ahmadi
    • , Sebastian Lippross
    •  & Hanns Ulrich Zeilhofer
  2. Institut für Anatomie, Krankenhausstrasse 9, Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany

    • Winfried L. Neuhuber

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Hanns Ulrich Zeilhofer.

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DOI

https://doi.org/10.1038/nn778

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