• Cristina Alba-Delgado, Meritxell Llorca-Torralba, Igor Horrillo, Jorge E Ortega, Juan Antonio Mico, Pilar Sánchez-Blázquez, J Javier Meana, and Esther Berrocoso.
• Neuropsychopharmacology Research Group, Department of Neuroscience, University of Cadiz, Cadiz, Spain.
• Biol. Psychiatry. 2013 Jan 1;73(1):54-62.

BackgroundPatients suffering chronic pain are at high risk of suffering long-lasting emotional disturbances characterized by persistent low mood and anxiety. We propose that this might be the result of a functional impairment in noradrenergic circuits associated with locus coeruleus (LC) and prefrontal cortex, where emotional and sensorial pain processes overlap.MethodsWe used a chronic constriction injury of sciatic nerve as a model of neuropathic pain in male Sprague-Dawley rats to assess the time-dependent changes that might potentially precipitate mood disorders (2, 7, 14, and 28 days after injury). This was measured through a combination of behavioral, electrophysiological, microdialysis, immunohistochemical, and Western blot assays.ResultsAs expected, nerve injury produced an early and stable decrease in sensorial pain threshold over the testing period. By contrast, long-term neuropathic pain (28 days after injury) resulted in an inability to cope with stressful situations, provoking depressive and anxiogenic-like behaviors, even more intense than the aversiveness associated with pain perception. The onset of these behavioral changes coincided with irruption of noradrenergic dysfunction, evident as: an increase in LC bursting activity; in tyrosine hydroxylase expression and that of the noradrenaline transporter; and enhanced expression and sensitivity of α2-adrenoceptors in the LC.ConclusionsLong-term neuropathic pain leads to anxio-depressive-like behaviors that are more predominant than the aversion of a painful experience. These changes are consistent with the impairment of noradrenergic system described in depressive disorders.Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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