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. 2013 Jan 1;73(1):54-62.
doi: 10.1016/j.biopsych.2012.06.033. Epub 2012 Jul 31.

Chronic pain leads to concomitant noradrenergic impairment and mood disorders

Cristina Alba-Delgado  1 , Meritxell Llorca-Torralba, Igor Horrillo, Jorge E Ortega, Juan Antonio Mico, Pilar Sánchez-Blázquez, J Javier Meana, Esther Berrocoso
Affiliations

Chronic pain leads to concomitant noradrenergic impairment and mood disorders

Cristina Alba-Delgado et al. Biol Psychiatry. .

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.

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