Corticotropin-Releasing Factor Mediates Pain-Induced Anxiety through the ERK1/2 Signaling Cascade in Locus Coeruleus Neurons.

Abstract

BACKGROUND:

The corticotropin-releasing factor is a stress-related neuropeptide that modulates locus coeruleus activity. As locus coeruleus has been involved in pain and stress-related patologies, we tested whether the pain-induced anxiety is a result of the corticotropin-releasing factor released in the locus coeruleus.

METHODS:

Complete Freund's adjuvant-induced monoarthritis was used as inflammatory chronic pain model. α-Helical corticotropin-releasing factor receptor antagonist was microinjected into the contralateral locus coeruleus of 4-week-old monoarthritic animals. The nociceptive and anxiety-like behaviors, as well as phosphorylated extracellular signal-regulated kinases 1/2 and corticotropin-releasing factor receptors expression, were quantified in the paraventricular nucleus and locus coeruleus.

RESULTS:

Monoarthritic rats manifested anxiety and increased phosphorylated extracellular signal-regulated kinases 1/2 levels in the locus coeruleus and paraventricular nucleus, although the expression of corticotropin-releasing factor receptors was unaltered. α-Helical corticotropin-releasing factor antagonist administration reversed both the anxiogenic-like behavior and the phosphorylated extracellular signal-regulated kinases 1/2 levels in the locus coeruleus.

CONCLUSIONS:

Pain-induced anxiety is mediated by corticotropin-releasing factor neurotransmission in the locus coeruleus through extracellular signal-regulated kinases 1/2 signaling cascade.

• Authors: Gisela Patrícia Borges, Juan Antonio Micó, Fani Lourença Neto, Esther Berrocoso
• Journal: The international journal of neuropsychopharmacology (Int J Neuropsychopharmacol) Vol. 18 Issue 8 (Feb 25 2015) ISSN: 1469-5111 [Electronic] England
• PMID: 25716783 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of CINP.

Chemical References

• Hormone Antagonists
• Peptide Fragments
• Receptors, Corticotropin-Releasing Hormone
• Freund's Adjuvant
• Corticotropin-Releasing Hormone
• corticotropin releasing hormone (9-41)

Topics

• Animals
• Anxiety Disorders (drug therapy, etiology, physiopathology)
• Arthritis, Experimental
• Chronic Pain (complications, drug therapy, physiopathology, psychology)
• Corticotropin-Releasing Hormone (metabolism, pharmacology)
• Freund's Adjuvant
• Hormone Antagonists (pharmacology)
• Locus Coeruleus (drug effects, physiopathology)
• MAP Kinase Signaling System (drug effects, physiology)
• Male
• Neurons (drug effects, physiology)
• Nociceptive Pain (drug therapy, etiology, physiopathology)
• Peptide Fragments (pharmacology)
• Phosphorylation (drug effects)
• Rats, Sprague-Dawley
• Receptors, Corticotropin-Releasing Hormone (antagonists & inhibitors, metabolism)