RESUMEN
Human neuroimaging studies and complementary animal experiments now identify the gross elements of the brain involved in the chronification of pain. We briefly review these advances in relation to somatic and orofacial persistent pain conditions. First, we emphasize the importance of reverse translational research for understanding chronic pain-that is, the power of deriving hypotheses directly from human brain imaging of clinical conditions that can be invasively and mechanistically studied in animal models. We then review recent findings demonstrating the importance of the emotional brain (i.e., the corticolimbic system) in the modulation of acute pain and in the prediction and amplification of chronic pain, contrasting this evidence with recent findings regarding the role of central sensitization in pain chronification, especially for orofacial pain. We next elaborate on the corticolimbic circuitry and underlying mechanisms that determine the transition to chronic pain. Given this knowledge, we advance a new mechanistic definition of chronic pain and discuss the clinical implications of this new definition as well as novel therapeutic potentials suggested by these advances.
Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Dolor Crónico/fisiopatología , Dolor Crónico/psicología , Emociones , Dolor Facial/fisiopatología , Dolor Facial/psicología , Sistema Límbico/fisiopatología , Neuroimagen , Animales , Humanos , Manejo del Dolor , Dimensión del DolorRESUMEN
Human brain imaging studies from various clinical cohorts show that chronic pain is associated with large-scale brain functional and morphological reorganization. However, how the rat whole-brain network is topologically reorganized to support persistent pain-like behavior following neuropathic injury remains unknown. Here we compare resting state fMRI functional connectivity-based whole-brain network properties between rats receiving spared nerve injury (SNI) vs. sham injury, at 5 days (n = 11 SNI; n = 12 sham) and 28 days (n = 11 SNI; n = 12 sham) post-injury. Similar to the human, the rat brain topological properties exhibited small world features and did not differ between SNI and sham. Local neural networks in SNI animals showed minimal disruption at day 5, and more extensive reorganization at day 28 post-injury. Twenty-eight days after SNI, functional connection changes were localized mainly to within the limbic system, as well as between the limbic and nociceptive systems. No connectivity changes were observed within the nociceptive network. Furthermore, these changes were lateralized and in proportion to the tactile allodynia exhibited by SNI animals. The findings establish that SNI is primarily associated with altered information transfer of limbic regions and provides a novel translational framework for understanding brain functional reorganization in response to a persistent neuropathic injury.
Asunto(s)
Sistema Límbico/fisiopatología , Neuralgia/fisiopatología , Animales , Dolor Crónico/fisiopatología , Modelos Animales de Enfermedad , Hiperalgesia/fisiopatología , Imagen por Resonancia Magnética/métodos , Masculino , Ratas , Ratas Sprague-Dawley , Descanso/fisiologíaRESUMEN
Activity of cortical local neuronal populations fluctuates continuously, and a large proportion of these fluctuations are shared across populations of neurons. Here we seek organizational rules that link these two phenomena. Using neuronal activity, as identified by functional MRI (fMRI) and for a given voxel or brain region, we derive a single measure of full bandwidth brain-oxygenation-level-dependent (BOLD) fluctuations by calculating the slope, α, for the log-linear power spectrum. For the same voxel or region, we also measure the temporal coherence of its fluctuations to other voxels or regions, based on exceeding a given threshold, Θ, for zero lag correlation, establishing functional connectivity between pairs of neuronal populations. From resting state fMRI, we calculated whole-brain group-averaged maps for α and for functional connectivity. Both maps showed similar spatial organization, with a correlation coefficient of 0.75 between the two parameters across all brain voxels, as well as variability with hodology. A computational model replicated the main results, suggesting that synaptic low-pass filtering can account for these interrelationships. We also investigated the relationship between α and structural connectivity, as determined by diffusion tensor imaging-based tractography. We observe that the correlation between α and connectivity depends on attentional state; specifically, α correlated more highly to structural connectivity during rest than while attending to a task. Overall, these results provide global rules for the dynamics between frequency characteristics of local brain activity and the architecture of underlying brain networks.
Asunto(s)
Encéfalo/anatomía & histología , Encéfalo/fisiología , Red Nerviosa/anatomía & histología , Red Nerviosa/fisiología , Adulto , Algoritmos , Atención/fisiología , Mapeo Encefálico , Imagen de Difusión Tensora/métodos , Análisis Discriminante , Imagen Eco-Planar/métodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Lineales , Imagen por Resonancia Magnética/métodos , Masculino , Modelos Estadísticos , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Distribución Normal , Oxígeno/sangre , Desempeño Psicomotor/fisiología , Procesos Estocásticos , Sinapsis/fisiologíaRESUMEN
Gonadotrophin-releasing hormone (GnRH) neurones located within the brain are the final neuroendocrine output regulating the reproductive hormone axis. Their small number and scattered distribution in the hypothalamus make them particularly difficult to study in vivo. The Cre/loxP system is a valuable tool to delete genes in specific cells and tissues. We report the production of two mouse lines that express the CRE bacteriophage recombinase in a GnRH-specific manner. The first line, the GnRH-CRE mouse, contains a transgene in which CRE is under the control of the murine GnRH promoter and targets CRE expression specifically to GnRH neurones in the hypothalamus. The second line, the GnRH-CRETeR mouse, uses the same murine GnRH promoter to target CRE expression to GnRH neurones, but is modified to be constitutively repressed by a tetracycline repressor (TetR) expressed from a downstream tetracycline repressor gene engineered within the transgene. GnRH neurone-specific CRE expression can therefore be induced by treatment with doxycycline which relieves repression by TetR. These GnRH-CRE and GnRH-CRETeR mice can be used to study the function of genes expressed specifically in GnRH neurones. The GnRH-CRETeR mouse can be used to study genes that may have distinct roles in reproductive physiology during the various developmental stages.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Hormona Liberadora de Gonadotropina/metabolismo , Integrasas/genética , Neuronas/metabolismo , Animales , Femenino , Fertilidad/genética , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Integrasas/metabolismo , Masculino , Ratones , Ratones Transgénicos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Recombinación Genética , Distribución Tisular , TransgenesRESUMEN
Presentamos un caso de litiasis vésico-uretral secundaria a calcificación de cuerpo extraño (gasa)1,2, dejado en celda prostática durante la cirugía abierta de próstata practicada doce años antes. En la revisión de la literatura podemos ver que la mayor parte de cuerpos extraños urinarios son secundarios a la introducción a través de la uretra de objetos con fines autoeróticos3-5, en pacientes normales o principalmente con trastornos psiquiátricos, y sólo una pequeña proporción es de causa iatrogénica, sobre todo en los últimos diez años (AU)