• Lidia Bravo, Cristina Alba-Delgado, Sonia Torres-Sanchez, Juan Antonio Mico, Fani L Neto, and Esther Berrocoso.
• Neuropsychopharmacology and Psychobiology Research Group, University of Cadiz, Cadiz, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
• Pain. 2013 Oct 1;154(10):2014-23.

AbstractStressful experiences seem to negatively influence pain perception through as yet unknown mechanisms. As the noradrenergic locus coeruleus (LC) nucleus coordinates many components of the stress response, as well as nociceptive transmission, we evaluated whether the sensory and affective dimension of chronic neuropathic pain worsens in situations of stress due to adaptive changes of LC neurons. Accordingly, male rats were socially isolated for 5 weeks, and in the last 2 weeks, neuropathic pain was induced by chronic constriction injury. In this situation of stress, chronic pain selectively heightened the animal's aversion to painful experiences (affective pain), as measured in the place escape/avoidance test, although no changes were observed in the sensory dimension of pain. In addition, electrophysiological recordings of LC neurons showed a low tonic but exacerbated nociceptive-evoked activity when the injured paw was stimulated. These changes were accompanied by an increase in tyrosine hydroxylase and gephyrin expression in the LC. Furthermore, intra-LC administration of bicuculline, a γ-aminobutyric acid-A receptor antagonist, attenuated the negative affective effects of pain. These data show that changes in the LC are greater than those expected from the simple summation of each independent factor (pain and stress), revealing mechanisms through which stressors may exacerbate pain perception without affecting the sensorial dimension.Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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