Pain exacerbates chronic mild stress-induced changes in noradrenergic transmission in rats.
Depression can influence pain and vice versa, yet the biological mechanisms underlying how one influences the pathophysiology of the other remains unclear. Dysregulation of locus coeruleus-noradrenergic transmission is implicated in both conditions, although it is not known whether this effect is exacerbated in cases of co-morbid depression and chronic pain. We studied locus coeruleus activity using immunofluorescence and electrophysiological approaches in rats subjected to unpredictable chronic mild stress (CMS, an experimental model of depression) and/or chronic constriction injury (CCI, a model of chronic neuropathic pain) for 2 weeks. CCI alone had no effect on any of the locus coeruleus parameters studied, while CMS led to a slight reduction in the electrophysiological activity of the locus coeruleus. Furthermore, CMS was associated with an increase in the number of tyrosine hydroxylase-positive cells in the locus coeruleus, although they were smaller in size. Interestingly, these effects of CMS were exacerbated when combined with CCI, even though no changes in the α2-adrenoreceptors or the noradrenaline transporter were observed in any group. Together, these findings suggest that CMS triggers several modifications in locus coeruleus-noradrenergic transmission that are exacerbated by co-morbid chronic pain.
Neuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cádiz, 11003 Cádiz, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28007 Madrid, Spain.
Lidia
L
Bravo
Neuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cádiz, 11003 Cádiz, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28007 Madrid, Spain.
Sonia
S
Torres-Sanchez
Neuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cádiz, 11003 Cádiz, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28007 Madrid, Spain.
Cristina
C
Alba-Delgado
Neuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cádiz, 11003 Cádiz, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28007 Madrid, Spain.
Juan A
JA
Mico
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28007 Madrid, Spain; Neuropsychopharmacology and Psychobiology Research Group, Psychobiology Area, Department of Psychology, University of Cadiz, Campus Universitario Rio San Pedro s/n, 11510 Cádiz, Spain. Electronic address: esther.berrocoso@uca.es.
Esther
E
Berrocoso
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D048429:Cell Size; D002908:Chronic Disease; D059350:Chronic Pain / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology; D015897:Comorbidity; D003866:Depressive Disorder / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D008125:Locus Coeruleus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009437:Neuralgia / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries; D013315:Stress, Psychological / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D050484:Norepinephrine Plasma Membrane Transport Proteins; D018341:Receptors, Adrenergic, alpha-2; D014446:Tyrosine 3-Monooxygenase
Comorbidity; Depression; Locus coeruleus; Pain; Stress; Tyrosine hydroxylase