title: Orofacial Neuropathic Pain Leads to a Hyporesponsive Barrel Cortex with Enhanced Structural Synaptic Plasticity.
abstract: Chronic pain is a long-lasting debilitating condition that is particularly difficult to treat due to the lack of identified underlying mechanisms. Although several key contributing processes have been described at the level of the spinal cord, very few studies have investigated the supraspinal mechanisms underlying chronic pain. Using a combination of approaches (cortical intrinsic imaging, immunohistochemical and behavioural analysis), our study aimed to decipher the nature of functional and structural changes in a mouse model of orofacial neuropathic pain, focusing on cortical areas involved in various pain components. Our results show that chronic neuropathic orofacial pain is associated with decreased haemodynamic responsiveness to whisker stimulation in the barrel field cortex. This reduced functional activation is likely due to the increased basal neuronal activity (measured indirectly using cFos and phospho-ERK immunoreactivity) observed in several cortical areas, including the contralateral barrel field, motor and cingulate cortices. In the same animals, immunohistochemical analysis of markers for active pre- or postsynaptic elements (Piccolo and phospho-Cofilin, respectively) revealed an increased immunofluorescence in deep cortical layers of the contralateral barrel field, motor and cingulate cortices. These results suggest that long-lasting orofacial neuropathic pain is associated with exacerbated neuronal activity and synaptic plasticity at the cortical level.
authors.affiliation: Brain Plasticity Unit, ESPCI, PSL Research University, 10 rue Vauquelin, 75005, Paris, France.|Centre National de la Recherche Scientifique, UMR 8249, 75005, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Thibault
authors.affiliation: Brain Plasticity Unit, ESPCI, PSL Research University, 10 rue Vauquelin, 75005, Paris, France.|Centre National de la Recherche Scientifique, UMR 8249, 75005, Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Rivière
authors.affiliation: Brain Plasticity Unit, ESPCI, PSL Research University, 10 rue Vauquelin, 75005, Paris, France.|Centre National de la Recherche Scientifique, UMR 8249, 75005, Paris, France.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Lenkei
authors.affiliation: Brain Plasticity Unit, ESPCI, PSL Research University, 10 rue Vauquelin, 75005, Paris, France.|Centre National de la Recherche Scientifique, UMR 8249, 75005, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Férézou
authors.affiliation: Brain Plasticity Unit, ESPCI, PSL Research University, 10 rue Vauquelin, 75005, Paris, France.|Centre National de la Recherche Scientifique, UMR 8249, 75005, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Pezet
mesh_terms: D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D059350:Chronic Pain / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004567:Electrodes, Implanted; D005157:Facial Pain / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005786:Gene Expression Regulation; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009437:Neuralgia / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009473:Neuronal Plasticity; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D013003:Somatosensory Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013238:Stereotaxic Techniques
chemical_list: D051339:Actin Depolymerizing Factors; D003598:Cytoskeletal Proteins; D009479:Neuropeptides; C498631:Pclo protein, mouse; D016760:Proto-Oncogene Proteins c-fos; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3