Citation

Alba-Delgado C, Llorca-Torralba M, Horrillo I, Ortega JE, Mico JA, Sánchez-Blázquez P, Meana JJ, Berrocoso E. Biol. Psychiatry 2013; 73(1): 54-62.

Affiliation

Neuropsychopharmacology Research Group, Department of Neuroscience, University of Cadiz, Cadiz, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.

Copyright

(Copyright © 2013, Elsevier Publishing)

DOI

10.1016/j.biopsych.2012.06.033

PMID

22854119

Abstract

BACKGROUND: Patients 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. METHODS: We 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. RESULTS: As 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. CONCLUSIONS: Long-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.

Language: en