@article{ref1,
title="Chronic pain leads to concomitant noradrenergic impairment and mood disorders",
journal="Biological psychiatry",
year="2013",
author="Alba-Delgado, Cristina and Llorca-Torralba, Meritxell and Horrillo, Igor and Ortega, Jorge E. and Mico, Juan Antonio and Sánchez-Blázquez, Pilar and Meana, J. Javier and Berrocoso, Esther",
volume="73",
number="1",
pages="54-62",
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.<p /> <p>Language: en</p>",
language="en",
issn="0006-3223",
doi="10.1016/j.biopsych.2012.06.033",
url="http://dx.doi.org/10.1016/j.biopsych.2012.06.033"
}