%0 Journal Article 
%A Alba Delgado, Cristina
%A Llorca Torralba, Meritxell
%A Horrillo, Igor
%A Ortega, Jorge E.
%A Micó Segura, Juan Antonio
%A Sánchez-Blázquez, Pilar
%A Meana, Javier
%A Berrocoso Domínguez, Esther María
%T Chronic pain leads to concomitant noradrenergic impairment and mood disorders
%D 2013
%@ 0006-3223

%U http://hdl.handle.net/10498/33329
%X 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.
%K α2-adrenoceptors
%K depression
%K locus coeruleus
%K neuropathic pain
%K noradrenaline
%K prefrontal cortex
%~ Universidad de Cádiz