Neuronal aldosterone elicits a distinct genomic response in pain signaling molecules contributing to inflammatory pain.

Journal of Neuroinflammation
Mohammed ShaquraMichael Schäfer

Abstract

Recently, mineralocorticoid receptors (MR) were identified in peripheral nociceptive neurons, and their acute antagonism was responsible for immediate and short-lasting (non-genomic) antinociceptive effects. The same neurons were shown to produce the endogenous ligand aldosterone by the enzyme aldosterone synthase. Here, we investigate whether endogenous aldosterone contributes to inflammation-induced hyperalgesia via the distinct genomic regulation of specific pain signaling molecules in an animal model of Freund's complete adjuvant (FCA)-induced hindpaw inflammation. Chronic intrathecal application of MR antagonist canrenoate-K (over 4 days) attenuated nociceptive behavior in rats with FCA hindpaw inflammation suggesting a tonic activation of neuronal MR by endogenous aldosterone. Consistently, double immunofluorescence confocal microscopy showed abundant co-localization of MR with several pain signaling molecules such as TRPV1, CGRP, Nav1.8, and trkA whose enhanced expression of mRNA and proteins during inflammation was downregulated following i.t. canrenoate-K. More importantly, inhibition of endogenous aldosterone production in peripheral sensory neurons by continuous intrathecal delivery of a specific aldosterone synthase...Continue Reading

References

Aug 1, 1976·Clinical Pharmacology and Therapeutics·L RamsayM Asbury
Mar 28, 1998·The Journal of Biological Chemistry·J S SilvestreC Delcayre
Jan 19, 2000·Steroids·F M Rogerson, P J Fuller
Nov 10, 2001·The Journal of Clinical Endocrinology and Metabolism·M J YoungJ W Funder
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jun 19, 2004·Current Opinion in Nephrology and Hypertension·Elise P Gomez-Sanchez
Jun 13, 2008·Nature Protocols·Thomas D Schmittgen, Kenneth J Livak
Apr 30, 2013·The Journal of Pain : Official Journal of the American Pain Society·Mohammed ShaquraMichael Schäfer
May 7, 2013·The Journal of Pain : Official Journal of the American Pain Society·Lingli LiangYuan-Xiang Tao
Nov 28, 2013·Molecular Pharmacology·Viola SpahnChristian Zöllner
Jun 20, 2014·Comprehensive Physiology·Elise Gomez-Sanchez, Celso E Gomez-Sanchez
Jan 17, 2017·Physiology & Behavior·Edo Ronald de Kloet, Marian Joëls
Apr 7, 2017·BMC Neuroscience·Marcin PiechotaRyszard Przewlocki
Jun 22, 2017·The Journal of Endocrinology·Marian Joëls, E Ronald de Kloet
Apr 3, 2019·International Journal of Molecular Sciences·Lisa T C M van WeertOnno C Meijer
Oct 11, 2019·Journal of the Endocrine Society·Anne-Sophie C A M KoningOnno C Meijer

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Methods Mentioned

BETA
nuclear translocation
PCR
electrophoresis
confocal microscopy
ELISA

Software Mentioned

Ensembl
Magellan
Image J
Java Image
Sigma Stat
SPSS
Zeiss Zen

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