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Int J Neuropsychopharmacol ; 18(8)2015 Feb 25.
Article in English | MEDLINE | ID: mdl-25716783

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.


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