TY - JOUR A1 - Mambretti, Egle M. A1 - Kistner, Katrin A1 - Mayer, Stefanie A1 - Massotte, Dominique A1 - Kieffer, Brigitte L. A1 - Hoffmann, Carsten A1 - Reeh, Peter W. A1 - Brack, Alexander A1 - Asan, Esther A1 - Rittner, Heike L. T1 - Functional and structural characterization of axonal opioid receptors as targets for analgesia JF - Molecular Pain N2 - Background Opioids are the gold standard for the treatment of acute pain despite serious side effects in the central and enteric nervous system. µ-opioid receptors (MOPs) are expressed and functional at the terminals of sensory axons, when activated by exogenous or endogenous ligands. However, the presence and function of MOP along nociceptive axons remains controversial particularly in naïve animals. Here, we characterized axonal MOPs by immunofluorescence, ultrastructural, and functional analyses. Furthermore, we evaluated hypertonic saline as a possible enhancer of opioid receptor function. Results Comparative immunolabeling showed that, among several tested antibodies, which all provided specific MOP detection in the rat central nervous system (CNS), only one monoclonal MOP-antibody yielded specificity and reproducibility for MOP detection in the rat peripheral nervous system including the sciatic nerve. Double immunolabeling documented that MOP immunoreactivity was confined to calcitonin gene-related peptide (CGRP) positive fibers and fiber bundles. Almost identical labeling and double labeling patterns were found using mcherry-immunolabeling on sciatic nerves of mice producing a MOP-mcherry fusion protein (MOP-mcherry knock-in mice). Preembedding immunogold electron microscopy on MOP-mcherry knock-in sciatic nerves indicated presence of MOP in cytoplasm and at membranes of unmyelinated axons. Application of [D-Ala\(^2\), N-MePhe\(^4\), Gly-ol]-enkephalin (DAMGO) or fentanyl dose-dependently inhibited depolarization-induced CGRP release from rat sciatic nerve axons ex vivo, which was blocked by naloxone. When the lipophilic opioid fentanyl was applied perisciatically in naïve Wistar rats, mechanical nociceptive thresholds increased. Subthreshold doses of fentanyl or the hydrophilic opioid DAMGO were only effective if injected together with hypertonic saline. In vitro, using β-arrestin-2/MOP double-transfected human embryonic kidney cells, DAMGO as well as fentanyl lead to a recruitment of β-arrestin-2 to the membrane followed by a β-arrestin-2 reappearance in the cytosol and MOP internalization. Pretreatment with hypertonic saline prevented MOP internalization. Conclusion MOPs are present and functional in the axonal membrane from naïve animals. Hypertonic saline acutely decreases ligand-induced internalization of MOP and thereby might improve MOP function. Further studies should explore potential clinical applications of opioids together with enhancers for regional analgesia. KW - µ-Opioid receptor KW - hypertonic solution KW - fentanyl KW - calcitonin gene-related peptide KW - DAMGO KW - internalization KW - peripheral nerve KW - ultrastructure Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145917 IS - 12 ER - TY - JOUR A1 - Achenbach, Leonard A1 - Le Hanneur, Malo A1 - Camenzind, Roland S. A1 - Bouyer, Michael A1 - Pottecher, Pierre A1 - Lafosse, Thibault T1 - Systematic bifocal decompression for isolated long thoracic nerve paresis: A case series of 12 patients JF - Interdisciplinary Neurosurgery N2 - To date, no consensus exists regarding the best surgical management of isolated, micro-traumatic long thoracic nerve (LTN) paresis. Our hypothesis was that a combined decompression of the LTN at two potential locations for entrapment would be effective in the management of dynamic LTN paresis. We report on twelve patients with isolated LTN parersis, with tenderness at two entrapment sites, who underwent bifocal LTN decompression after undergoing unsuccessful conservative treatment for at least 6 months; all patients had preoperative electrodiagnostic studies that confirmed the paresis and ruled out peripheral neuritis. Clinical and electrical improvements were observed in eight patients (67%) regarding shoulder flexion, shoulder abduction, and Quick-DASH scores. Four patients (33%) did not improve after surgery. The results corroborate our hypothesis that a bifocal LTN decompression can be an effective and reliable therapeutic option in more than half of a very selective patient population suffering from serratus anterior muscle deficiency. KW - entrapment, traction KW - serratus anterior KW - scapular winging KW - scapula alata KW - dyskinesia KW - peripheral nerve KW - nerve compression KW - micro-traumatic KW - neurolysis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265085 VL - 27 ER -