title: Acute mechanical sensitization of peripheral nociceptors by aldosterone through non-genomic activation of membrane bound mineralocorticoid receptors in naive rats.
abstract: Recently, there is increasing interest in the role of peripheral mineralocorticoid receptors (MR) to modulate pain, but their localization in neurons and glia of the periphery and their distinct involvement in pain control remains elusive. In naive Wistar rats our double immunofluorescence confocal microscopy of the spinal cord, dorsal root ganglia, sciatic nerve and innervated skin revealed that MR predominantly colocalized with calcitonin-gene-related peptide (CGRP)- and trkA-immunoreactive (IR) nociceptive neurons and only marginally with myelinated trkB-IR mechanoreceptive and trkC-IR proprioreceptive neurons underscoring a pivotal role for MR in the modulation of pain. MR could not be detected in Schwann cells, satellite cells, and astrocytes and only scarcely in spinal microglia cells excluding a relevant functional role of glia-derived MR at least in naïve rats. Intrathecal (i.t.) and intraplantar (i.pl.) application of increasing doses of the MR selective agonist aldosterone acutely increased nociceptive behavior which was reversible by a MR selective antagonist and most likely due to non-genomic effects. This was further substantiated by the first identification of membrane bound MR specific binding sites in sensory neurons of dorsal root ganglia and spinal cord. Therefore, a crucial role of MR on nociceptive neurons but not on glia cells and their impact on nociceptive behavior most likely due to immediate non-genomic effects has to be considered under normal but more so under pathological conditions in future studies.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Charité University Berlin, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shaqura
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Charité University Berlin, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany.
authors.forename: Xiongjuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Charité University Berlin, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Al-Madol
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Charité University Berlin, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Tafelski
authors.affiliation: Department of Anaesthesiology, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Beyer-Koczorek
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Charité University Berlin, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany. Electronic address: shaaban.mousa@charite.de.
authors.forename: Shaaban A
authors.initials: SA
authors.lastname: Mousa
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Charité University Berlin, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfer
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D023281:Genomics; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000378:metabolism*; D010812:Physical Stimulation / Q000379:methods; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000819:agonists / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
chemical_list: D018161:Receptors, Mineralocorticoid; D000450:Aldosterone
keywords: Glia; Mineralocorticoid receptor; Nociceptive neuron; Non-genomic effect