Social stress exacerbates the aversion to painful experiences in rats exposed to chronic pain: The role of the locus coeruleus

• Published in: Pain (Amsterdam) Vol. 154; no. 10; pp. 2014 - 2023
• Main Authors: Bravo, Lidia, Alba-Delgado, Cristina, Torres-Sanchez, Sonia, Mico, Juan Antonio, Neto, Fani L., Berrocoso, Esther
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Elsevier B.V 01-10-2013; Lippincott Williams & Wilkins, Inc; Elsevier
• Subjects: Affective pain; Animals; Avoidance Learning - physiology; Biological and medical sciences; Chronic Pain - physiopathology; Chronic Pain - psychology; Fundamental and applied biological sciences. Psychology; Gephyrin; Locus coeruleus; Locus Coeruleus - physiology; Male; Medical sciences; Nervous system involvement in other diseases. Miscellaneous; Neurology; Neuropathic pain; Pain Measurement - methods; Pain Measurement - psychology; Rats; Rats, Sprague-Dawley; Social Isolation - psychology; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Stress; Stress, Psychological - physiopathology; Stress, Psychological - psychology; Tyrosine hydroxylase; Vertebrates: nervous system and sense organs; Affective pain; Tyrosine hydroxylase; Gephyrin; Stress; Locus coeruleus; Neuropathic pain; Affect affectivity; Rat; Enzyme; Rodentia; Central nervous system; Tyrosine 3-monooxygenase; Encephalon; Vertebrata; Chronic; Mammalia; Animal; Oxidoreductases
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/j.pain.2013.06.021

Isolation selectively exerts a negative influence on the affective pain experience by increased evoked activity of the locus coeruleus under neuropathic pain conditions.
Stressful 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.