title: Increased fronto-hippocampal connectivity in the Prrxl1 knockout mouse model of congenital hypoalgesia.
abstract: Despite the large number of studies addressing how prolonged painful stimulation affects brain functioning, there are only a handful of studies aimed at uncovering if persistent conditions of reduced pain perception would also result in brain plasticity. Permanent hypoalgesia induced by neonatal injection of capsaicin or carrageenan has already been shown to affect learning and memory and to induce alterations in brain gene expression. In this study, we used the Prrxl1 model of congenital mild hypoalgesia to conduct a detailed study of the neurophysiological and behavioral consequences of reduced pain experience. Prrxl1 knockout animals are characterized by selective depletion of small diameter primary afferents and abnormal development of the superficial dorsal laminae of the spinal cord, resulting in diminished pain perception but normal tactile and motor behaviour. Behavioral testing of Prrxl1 mice revealed that these animals have reduced anxiety levels, enhanced memory performance, and improved fear extinction. Neurophysiological recordings from awake behaving Prrxl1 mice show enhanced altered fronto-hippocampal connectivity in the theta- and gamma-bands. Importantly, although inflammatory pain by Complete Freund Adjuvant injection caused a decrease in fronto-hippocampal connectivity in the wild-type animals, Prrxl1 mice maintained the baseline levels. The onset of inflammatory pain also reverted the differences in forebrain expression of stress- and monoamine-related genes in Prrxl1 mice. Altogether our results suggest that congenital hypoalgesia may have an effect on brain plasticity that is the inverse of what is usually observed in animal models of chronic pain.
authors.affiliation: Departamento de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.|Instituto de Biologia Molecular e Celular-IBMC, Universidade do Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde-i3S, Universidade do Porto, Porto, Portugal.
authors.forename: Clara
authors.initials: C
authors.lastname: Monteiro
authors.affiliation: Departamento de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.|Instituto de Biologia Molecular e Celular-IBMC, Universidade do Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde-i3S, Universidade do Porto, Porto, Portugal.
authors.forename: Helder
authors.initials: H
authors.lastname: Cardoso-Cruz
authors.affiliation: Departamento de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.|Instituto de Biologia Molecular e Celular-IBMC, Universidade do Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde-i3S, Universidade do Porto, Porto, Portugal.
authors.forename: Mariana
authors.initials: M
authors.lastname: Matos
authors.affiliation: Departamento de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.|Instituto de Biologia Molecular e Celular-IBMC, Universidade do Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde-i3S, Universidade do Porto, Porto, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Dourado
authors.affiliation: Departamento de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.|Instituto de Biologia Molecular e Celular-IBMC, Universidade do Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde-i3S, Universidade do Porto, Porto, Portugal.
authors.forename: Deolinda
authors.initials: D
authors.lastname: Lima
authors.affiliation: Departamento de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.|Instituto de Biologia Molecular e Celular-IBMC, Universidade do Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde-i3S, Universidade do Porto, Porto, Portugal.
authors.forename: Vasco
authors.initials: V
authors.lastname: Galhardo
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology; D004195:Disease Models, Animal; D004594:Electrophysiology; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000235:genetics; D005620:Freund's Adjuvant / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D018398:Homeodomain Proteins / Q000235:genetics; D006987:Hypesthesia / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009434:Neural Pathways / Q000503:physiopathology*; D010147:Pain Measurement; D021641:Recognition, Psychology / Q000502:physiology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C433766:Prrxl1 protein, mouse; D014157:Transcription Factors; D005620:Freund's Adjuvant