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Pro- versus Antinociceptive Nongenomic Effects of Neuronal Mineralocorticoid versus Glucocorticoid Receptors during Rat Hind Paw Inflammation
- Source :
- Anesthesiology. 128:796-809
- Publication Year :
- 2018
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2018.
-
Abstract
- Background In naive rats, corticosteroids activate neuronal membrane–bound glucocorticoid and mineralocorticoid receptors in spinal cord and periphery to modulate nociceptive behavior by nongenomic mechanisms. Here we investigated inflammation-induced changes in neuronal versus glial glucocorticoid and mineralocorticoid receptors and their ligand-mediated nongenomic impact on mechanical nociception in rats. Methods In Wistar rats (n = 5 to 7/group) with Freund’s complete adjuvant hind paw inflammation, we examined glucocorticoid and mineralocorticoid receptor expression in spinal cord and peripheral sensory neurons versus glial using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, immunohistochemistry, and radioligand binding. Moreover, we explored the expression of mineralocorticoid receptors protecting enzyme 11-betahydroxysteroid dehydrogenase type 2 as well as the nociceptive behavioral changes after glucocorticoid and mineralocorticoid receptors agonist or antagonist application. Results Hind paw inflammation resulted in significant upregulation of glucocorticoid receptors in nociceptive neurons of spinal cord (60%) and dorsal root ganglia (15%) as well as mineralocorticoid receptors, while corticosteroid plasma concentrations remained unchanged. Mineralocorticoid (83 ± 16 fmol/mg) but not glucocorticoid (104 ± 20 fmol/mg) membrane binding sites increased twofold in dorsal root ganglia concomitant with upregulated 11-betahydroxysteroid dehydrogenase type 2 (43%). Glucocorticoid and mineralocorticoid receptor expression in spinal microglia and astrocytes was small. Importantly, glucocorticoid receptor agonist dexamethasone or mineralocorticoid receptor antagonist canrenoate-K rapidly and dose-dependently attenuated nociceptive behavior. Isobolographic analysis of the combination of both drugs showed subadditive but not synergistic or additive effects. Conclusions The enhanced mechanical sensitivity of inflamed hind paws accompanied with corticosteroid receptor upregulation in spinal and peripheral sensory neurons was attenuated immediately after glucocorticoid receptor agonist and mineralocorticoid receptor antagonist administration, suggesting acute nongenomic effects consistent with detected membrane-bound corticosteroid receptors.
- Subjects :
- Male
Agonist
medicine.medical_specialty
medicine.drug_class
Freund's Adjuvant
03 medical and health sciences
Receptors, Glucocorticoid
0302 clinical medicine
Glucocorticoid receptor
Mineralocorticoid receptor
030202 anesthesiology
Internal medicine
medicine
Animals
Rats, Wistar
Receptor
Glucocorticoids
Dexamethasone
Mineralocorticoid Receptor Antagonists
Pain Measurement
Inflammation
Analgesics
business.industry
Nociceptors
Hindlimb
Rats
Receptors, Mineralocorticoid
Anesthesiology and Pain Medicine
Nociception
Endocrinology
Mineralocorticoid
business
hormones, hormone substitutes, and hormone antagonists
030217 neurology & neurosurgery
Glucocorticoid
medicine.drug
Subjects
Details
- ISSN :
- 00033022
- Volume :
- 128
- Database :
- OpenAIRE
- Journal :
- Anesthesiology
- Accession number :
- edsair.doi.dedup.....dcdcef57d45f57ce566018cf7102d277
- Full Text :
- https://doi.org/10.1097/aln.0000000000002087