title: 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.affiliation: Neuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cádiz, Cádiz, Spain (Ms Borges and Dr Micó); Departamento de Biologia Experimental, Centro de Investigação Médica da Faculdade de Medicina da Universidade do Porto, Porto, Portugal (Ms Borges and Dr Neto); Grupo de Morfofisiologia do Sistema Somatossensitivo, Instituto de Biologia Molecular e Celular, Porto, Portugal (Ms Borges and Dr Neto); Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain (Drs Micó and Berrocoso); Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cádiz, Cádiz, Spain (Dr Berrocoso).
authors.forename: Gisela Patrícia
authors.initials: GP
authors.lastname: Borges
authors.affiliation: Neuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cádiz, Cádiz, Spain (Ms Borges and Dr Micó); Departamento de Biologia Experimental, Centro de Investigação Médica da Faculdade de Medicina da Universidade do Porto, Porto, Portugal (Ms Borges and Dr Neto); Grupo de Morfofisiologia do Sistema Somatossensitivo, Instituto de Biologia Molecular e Celular, Porto, Portugal (Ms Borges and Dr Neto); Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain (Drs Micó and Berrocoso); Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cádiz, Cádiz, Spain (Dr Berrocoso).
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Micó
authors.affiliation: Neuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cádiz, Cádiz, Spain (Ms Borges and Dr Micó); Departamento de Biologia Experimental, Centro de Investigação Médica da Faculdade de Medicina da Universidade do Porto, Porto, Portugal (Ms Borges and Dr Neto); Grupo de Morfofisiologia do Sistema Somatossensitivo, Instituto de Biologia Molecular e Celular, Porto, Portugal (Ms Borges and Dr Neto); Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain (Drs Micó and Berrocoso); Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cádiz, Cádiz, Spain (Dr Berrocoso).
authors.forename: Fani Lourença
authors.initials: FL
authors.lastname: Neto
authors.affiliation: Neuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cádiz, Cádiz, Spain (Ms Borges and Dr Micó); Departamento de Biologia Experimental, Centro de Investigação Médica da Faculdade de Medicina da Universidade do Porto, Porto, Portugal (Ms Borges and Dr Neto); Grupo de Morfofisiologia do Sistema Somatossensitivo, Instituto de Biologia Molecular e Celular, Porto, Portugal (Ms Borges and Dr Neto); Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain (Drs Micó and Berrocoso); Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cádiz, Cádiz, Spain (Dr Berrocoso). esther.berrocoso@uca.es.
authors.forename: Esther
authors.initials: E
authors.lastname: Berrocoso
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D001169:Arthritis, Experimental; D059350:Chronic Pain / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D005620:Freund's Adjuvant; D006727:Hormone Antagonists / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects / Q000503:physiopathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D059226:Nociceptive Pain / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D006727:Hormone Antagonists; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D005620:Freund's Adjuvant; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)
keywords: anxiety; corticotropin-releasing factor; locus coeruleus; pERK1/2; pain