title: Noradrenaline-mediated facilitation of inhibitory synaptic transmission in the dorsal horn of the rat spinal cord involves interlaminar communications.
abstract: In the dorsal horn of the spinal cord (DH), noradrenaline (NA) is released by axons originating from the locus coeruleus and induces spinal analgesia, the mechanisms of which are poorly understood. Here, the effects of NA on synaptic transmission in the deep laminae (III-V) of the DH were characterized. It was shown that exogenously applied, as well as endogenously released, NA facilitated inhibitory [γ-aminobutyric acid (GABA)ergic and glycinergic] synaptic transmission in laminae III-IV of the DH by activating α1-, α2- and β-adrenoceptors (ARs). In contrast, NA had no effect on excitatory (glutamatergic) synaptic transmission. Physical interruption of communications between deep and more superficial laminae (by a mechanical transection between laminae IV and V) totally blocked the effects of α2-AR agonists and strongly reduced the effects of α1-AR agonists on inhibitory synaptic transmission in laminae III-IV without directly impairing synaptic release of GABA or glycine from neurons. Short-term pretreatment of intact spinal cord slices with the glial cell metabolism inhibitor fluorocitrate or pharmacological blockade of ionotropic glutamate and ATP receptors mimicked the consequences of a mechanical transection between laminae IV and V. Taken together, the current results indicate that the facilitation of inhibitory synaptic transmission in laminae III-IV of the DH by NA requires functional interlaminar connections between deep and more superficial laminae, and might strongly depend on glia to neuron interactions. These interlaminar connections and glia to neuron interactions could represent interesting targets for analgesic strategies.
authors.affiliation: Centre National de la Recherche Scientifique (CNRS UPR 3212), Institut des Neurosciences Cellulaires et Intégratives, 5 rue Blaise Pascal, 67084, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors.forename: Frederik
authors.initials: F
authors.lastname: Seibt
authors.affiliation: Centre National de la Recherche Scientifique (CNRS UPR 3212), Institut des Neurosciences Cellulaires et Intégratives, 5 rue Blaise Pascal, 67084, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Schlichter
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009457:Neuroglia / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D018091:Receptors, AMPA / Q000502:physiology; D011941:Receptors, Adrenergic / Q000502:physiology; D018092:Kainic Acid Receptors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000502:physiology; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000502:physiology*
chemical_list: D000322:Adrenergic Agonists; D009638:Norepinephrine; D018091:Receptors, AMPA; D011941:Receptors, Adrenergic; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D018048:Receptors, Purinergic P2
keywords: adrenoceptor; glial cells; glycine; inhibitory postsynaptic current; γ-aminobutyric acid