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

Content Provider	Springer Nature : BioMed Central
Author	Shaqura, Mohammed Li, Li Mohamed, Doaa M. Li, Xiongjuan Treskatsch, Sascha Buhrmann, Constanze Shakibaei, Mehdi Beyer, Antje Mousa, Shaaban A. Schäfer, Michael
Abstract	Background 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. Methods 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. Results 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 inhibitor prevented the inflammation-induced enhanced transcriptional expression of TRPV1, CGRP, Nav1.8, and trkA and subsequently attenuated nociceptive behavior. Evidence for such a genomic effect of endogenous aldosterone was supported by the demonstration of an enhanced nuclear translocation of MR in peripheral sensory dorsal root ganglia (DRG) neurons. Conclusion Taken together, chronic inhibition of local production of aldosterone by its processing enzyme aldosterone synthase within peripheral sensory neurons may contribute to long-lasting downregulation of specific pain signaling molecules and may, thus, persistently reduce inflammation-induced hyperalgesia.
Related Links	https://jneuroinflammation.biomedcentral.com/counter/pdf/10.1186/s12974-020-01864-8.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
ISSN	17422094
DOI	10.1186/s12974-020-01864-8
Journal	Journal of Neuroinflammation
Issue Number	1
Volume Number	17
Language	English
Publisher	BioMed Central
Publisher Date	2020-06-12
Access Restriction	Open
Subject Keyword	Neurosciences Neurology Neurobiology Immunology Aldosterone synthase Pain signaling molecules Sensory neurons
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology Cellular and Molecular Neuroscience Neurology
Journal Impact Factor	9.3/2023
5-Year Journal Impact Factor	9.8/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Prostanoid signaling in retinal cells elicits inflammatory responses relevant to early-stage diabetic retinopathy

Vesicular HMGB1 release from neurons stressed with spreading depolarization enables confined inflammatory signaling to astrocytes

Acetaminophen inhibits neuronal inflammation and protects neurons from oxidative stress

SAFit2 reduces neuroinflammation and ameliorates nerve injury-induced neuropathic pain

SDF1–CXCR4 signaling contributes to persistent pain and hypersensitivity via regulating excitability of primary nociceptive neurons: involvement of ERK-dependent Nav1.8 up-regulation

Microglia sustain anterior cingulate cortex neuronal hyperactivity in nicotine-induced pain

Correction to: C3aR signaling and gliosis in response to neurodevelopmental damage in the cerebellum

Localization of brain neuronal IL-1R1 reveals specific neural circuitries responsive to immune signaling

Microbial BMAA elicits mitochondrial dysfunction, innate immunity activation, and Alzheimer’s disease features in cortical neurons

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

Similar Documents

Prostanoid signaling in retinal cells elicits inflammatory responses relevant to early-stage diabetic retinopathy

Vesicular HMGB1 release from neurons stressed with spreading depolarization enables confined inflammatory signaling to astrocytes

Acetaminophen inhibits neuronal inflammation and protects neurons from oxidative stress

SAFit2 reduces neuroinflammation and ameliorates nerve injury-induced neuropathic pain

SDF1–CXCR4 signaling contributes to persistent pain and hypersensitivity via regulating excitability of primary nociceptive neurons: involvement of ERK-dependent Nav1.8 up-regulation

Microglia sustain anterior cingulate cortex neuronal hyperactivity in nicotine-induced pain

Correction to: C3aR signaling and gliosis in response to neurodevelopmental damage in the cerebellum

Localization of brain neuronal IL-1R1 reveals specific neural circuitries responsive to immune signaling

Microbial BMAA elicits mitochondrial dysfunction, innate immunity activation, and Alzheimer’s disease features in cortical neurons

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