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Neuronal and glial localization of the cannabinoid-1 receptor in the superficial spinal dorsal horn of the rodent spinal cord

Authors

  • Zoltán Hegyi,

    1. Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, H-4032 Hungary
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  • Gréta Kis,

    1. Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, H-4032 Hungary
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  • Krisztina Holló,

    1. Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, H-4032 Hungary
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  • Catherine Ledent,

    1. IRIBHN, Universitté Libre de Bruxelles, B-1070 Brussels, Belgium
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  • Miklós Antal

    1. Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, H-4032 Hungary
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Dr M. Antal, as above.
E-mail: antal@chondron.anat.dote.hu

Abstract

A long line of experimental evidence indicates that endogenous cannabinoid mechanisms play important roles in nociceptive information processing in various areas of the nervous system including the spinal cord. Although it is extensively documented that the cannabinoid-1 receptor (CB1-R) is strongly expressed in the superficial spinal dorsal horn, its cellular distribution is poorly defined, hampering our interpretation of the effect of cannabinoids on pain processing spinal neural circuits. Thus, we investigated the cellular distribution of CB1-Rs in laminae I and II of the rodent spinal dorsal horn with immunocytochemical methods. Axonal varicosities revealed a strong immunoreactivity for CB1-R, but no CB1-R expression was observed on dendrites and perikarya of neurons. Investigating the co-localization of CB1-R with markers of peptidergic and non-peptidergic primary afferents, and axon terminals of putative glutamatergic and GABAergic spinal neurons we found that nearly half of the peptidergic (immunoreactive for calcitonin gene-related peptide) and more than 20% of the non-peptidergic (binding isolectin B4) nociceptive primary afferents, more than one-third and approximately 20% of the axon terminals of putative glutamatergic (immunoreactive for vesicular glutamate transporter 2) and GABAergic (immunoreactive for glutamic acid decarboxylase; GAD65 and/or GAD67) spinal interneurons, respectively, were positively stained for CB1-R. In addition to axon terminals, almost half of the astrocytic (immunoreactive for glial fibrillary acidic protein) and nearly 80% of microglial (immunoreactive for CD11b) profiles were also immunolabeled for CB1-R. The findings suggest that the activity-dependent release of endogenous cannabinoids activates a complex signaling mechanism in pain processing spinal neural circuits into which both neurons and glial cells may contribute.

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