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Dynamic balance of metabotropic inputs causes dorsal horn neurons to switch functional states

Nature Neuroscience volume 6, pages 274–281 (2003)Cite this article

Abstract

Sensory relay structures in the spinal cord dorsal horn are now thought to be active processing structures that function before supraspinal sensory integration. Dorsal horn neurons directly receive nociceptive (pain) signals from the periphery, express a high degree of functional plasticity and are involved in long-term sensitization and chronic pain. We show here that deep dorsal horn neurons (DHNs) in Wistar rats can switch their intrinsic firing properties from tonic to plateau or endogenous bursting patterns, depending upon the balance of control by metabotropic glutamate (mGlu) and GABAB receptors. We further show that this modulation acts on at least one common target, the inwardly rectifying potassium channel (Kir3). Finally, we found that these firing modes correspond to specific functional states of information transfer in which dorsal horn neurons can faithfully transmit, greatly enhance or block the transfer of nociceptive information.

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Figure 1: Deep DHNs show three modes of firing.
Figure 2: Antagonistic modulation of a Kir current.
Figure 3: Deep DHNs receive modulatory inputs and express Kir3 channels.
Figure 4: The three DHN firing modes correspond to different states of sensory information transfer.
Figure 5: Variations of sensory information transfer as a function of input frequency and pattern.

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Acknowledgements

We are grateful to S. El Mestikawy (INSERM U513) for the gift of the anti-VGluT antibodies and to S. Shefchyk (SCRC, Univ. of Manitoba Winnipeg) for helpful discussions and careful reading of the manuscript. This work was supported by grants from the Conseil Régional d'Aquitaine (20010301213), the Direction Générale des Armées (01.34.012.00470.75.01), the Institut UPSA de la Douleur, the Fondation de la Recherche Médicale (ARI20010406005/1) and the Fondation Singer-Polignac.

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  1. Valérie Morisset

    Present address: HW1712, GlaxoSmithKline, NFSP North, Third Avenue, Harlow, Essex, CM195AW, UK

  2. Dominique Derjean and Sandrine Bertrand: The first two authors contributed equally to this work.

Authors and Affiliations

  1. INSERM E0358, Physiopathologie des Réseaux Neuronaux Médullaires, Institut François Magendie, Université Bordeaux 2, Bordeaux, France

    Dominique Derjean, Sandrine Bertrand, Gwendal Le Masson, Marc Landry & Frédéric Nagy

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Correspondence to Frédéric Nagy.

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Derjean, D., Bertrand, S., Le Masson, G. et al. Dynamic balance of metabotropic inputs causes dorsal horn neurons to switch functional states. Nat Neurosci 6, 274–281 (2003). https://doi.org/10.1038/nn1016

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