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The Journal of Neuroscience, January 18, 2006, 26(3):953-962; doi:10.1523/JNEUROSCI.3598-05.2006
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Cellular/Molecular
Morphine and Pain-Related Stimuli Enhance Cell Surface Availability of Somatic  -Opioid Receptors in Rat Dorsal Root Ganglia
Louis Gendron,1
Anna Lisa Lucido,1
Françoise Mennicken,2
Dajan O'Donnell,2
Jean-Pierre Vincent,3
Thomas Stroh,1 and
Alain Beaudet1
1Department of Neurology and Neurosurgery, Montréal Neurological Institute, McGill University, Montréal, Québec, Canada H3A 2B4, 2AstraZeneca R&D Montréal, Ville St-Laurent, Québec, Canada H4S 1Z9, and 3Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097 du Centre National de la Recherche Scientifique, 06560 Valbonne, France
The present study demonstrates that perikaryal -opioid receptors (ORs) in rat dorsal root ganglion (DRG) neurons bind and internalize opioid ligands circulating in the CSF. Using confocal and electron microscopy, we found that prolonged morphine treatment increased the cell surface density of these perikaryal ORs and, by way of consequence, receptor-mediated internalization of the fluorescent deltorphin (DLT) analog  -Bodipy 576/589 deltorphin-I 5-aminopentylamide (Fluo-DLT) in all three types of DRG neurons (small, medium, and large). In contrast, chronic inflammatory pain induced by the injection of complete Freund's adjuvant (CFA) into one hindpaw selectively increased Fluo-DLT internalization in small and medium-sized DRG neurons ipsilateral to the inflammation. Based on our previous studies in the spinal cord of µ-opioid receptor (µOR) knock-out mice, it may be assumed that the enhanced membrane recruitment of ORs observed after sustained morphine is attributable to stimulation of µORs. However, the selectivity of the effect induced by inflammatory pain suggests that it involves a different mechanism, namely a modality-specific and pain-related activation of C and A fibers. Indeed, stimulation by capsaicin of transient receptor potential vanilloid 1 receptors, which are selectively expressed by small diameter (< 600 µm2) DRG neurons, increased Fluo-DLT internalization exclusively in this cell population. The present results, therefore, demonstrate that DRG neurons express perikaryal ORs accessible to CSF-circulating ligands and that the density and, hence, presumably also the responsiveness, of these receptors may be modulated by both pain-related stimuli and sustained exposure to µOR agonists.
Key words: -opioid receptor; deltorphin; dorsal root ganglia; targeting; chronic inflammation; receptor internalization; fluorescent ligand
Received Aug 24, 2005;
revised November 22, 2005;
accepted November 23, 2005.
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