1. The Anterior Cingulate Cortex Is a Critical Hub for Pain-Induced Depression
- Author
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Jim Sellmeijer, Elisabeth Waltisperger, Ipek Yalcin, Michel Barrot, Sylvain Hugel, Florent Barthas, Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Male ,Pain Threshold ,Patch-Clamp Techniques ,[SDV]Life Sciences [q-bio] ,Mice, Transgenic ,Sensory system ,Stimulation ,Anxiety ,Motor Activity ,Insular cortex ,Gyrus Cinguli ,Conditioning, Psychological ,medicine ,Animals ,Chronic stress ,Ibotenic Acid ,ComputingMilieux_MISCELLANEOUS ,Biological Psychiatry ,Anterior cingulate cortex ,Cerebral Cortex ,Depressive Disorder ,Chronic pain ,medicine.disease ,Immunohistochemistry ,Sciatic Nerve ,Mice, Inbred C57BL ,Optogenetics ,Disease Models, Animal ,medicine.anatomical_structure ,Allodynia ,Hyperalgesia ,Anesthesia ,Neuropathic pain ,Neuralgia ,Chronic Pain ,medicine.symptom ,Psychology ,Neuroscience - Abstract
Background Besides chronic stress, chronic pain is a prevalent determinant for depression. Changes induced in specific brain regions by sustained pain may alter the processing of affective information, thus resulting in anxiodepressive disorders. Here, we compared the role of the anterior cingulate cortex (ACC) and the posterior insular cortex in the anxiodepressive, sensory, and affective aspects of chronic pain. Methods Neuropathic pain was induced by cuffing the right sciatic nerve of C57BL/6J mice. Lesions were performed by local injection of ibotenic acid and chronic activation of the ACC by optogenetic stimulation. Anxiodepressive-related behaviors were evaluated through the novelty suppressed feeding, marble burying, splash, and forced swimming tests. Mechanical thresholds were determined using von Frey filaments, and the relief of spontaneous pain was determined by using place conditioning. Results The ACC lesion prevented the anxiodepressive consequences of chronic pain without affecting the sensory mechanical allodynia. Conversely, the tonic or spontaneous pain and the anxiodepressive consequences of pain remained present after posterior insular cortex lesion, even though the mechanical allodynia was suppressed. Furthermore, optogenetic stimulation of the ACC was sufficient to induce anxiety and depressive-like behaviors in naive animals. Conclusions Our results show that, at cortical level, the sensory component of chronic pain remains functionally segregated from its affective and anxiodepressive components. Spontaneous tonic pain and evoked allodynia can be experimentally dissociated. Furthermore, the ACC appears as a critical hub for mood disorders, including for the anxiodepressive consequences of chronic pain, and thus constitutes an important target for divulging the underlying mechanism.
- Published
- 2015