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LOS FENOMENOS INFLAMATORIOS NEUROGENICOS SON UN NUEVO BLANCO TERAPEUTICO EN LA MIGRAÑA

LOS FENOMENOS INFLAMATORIOS NEUROGENICOS SON UN NUEVO BLANCO TERAPEUTICO EN LA MIGRAÑA

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Uno de los principales mecanismos patogénicos de las crisis migrañosas es la activación de las vías trigeminovasculares, que constituyen el blanco terapéutico de diversos fármacos efectivos para tratar la migraña. Algunos datos recientes sustentan la presencia de eventos inflamatorios transitorios, autolimitados, de origen neurogénico, subsiguientes a la activación trigeminovascular, los que pueden ser antagonizados mediante opciones terapéuticas establecidas o experimentales para la migraña aguda.
sarchielli9.jpg Autor:
Paola Sarchielli
Columnista Experto de SIIC
Artículos publicados por Paola Sarchielli
Coautores
Francesca Coppola* Cristiana Rossi* Antonio Baldi* Ilenia Corbelli* Katiuscia Nardi* Monica Acciarresi* 
Doctor of Medicine, University of Perugia, Perugia, Italia*
Recepción del artículo
26 de Septiembre, 2006
Aprobación
13 de Diciembre, 2006
Primera edición
27 de Abril, 2007
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
Se considera que la activación de las vías trigeminovasculares desempeña un papel crucial en la inducción y el mantenimiento de la crisis migrañosa y se ha propuesto que la inflamación neurogénica, consecutiva a dicha activación, es uno de los mecanismos patogénicos principales de la cefalea. La liberación del péptido relacionado con el gen de calcitonina (CGRP) y la producción de óxido nítrico (NO) son los eventos más importantes del proceso inflamatorio neurogénico subyacente a la fase de dolor de la migraña. Los hallazgos firmes provenientes de modelos animales y de la investigación clínica se centran en los agentes antimigrañosos que limitan los eventos inducidos por la activación de las neuronas trigeminales, en particular, la liberación de CGRP y la vasodilatación a nivel meníngeo. Tales compuestos incluyen fármacos efectivos para el tratamiento agudo de la migraña, como los triptanos, los derivados del cornezuelo de centeno, los agentes antiinflamatorios no esteroides o los inhibidores de la ciclooxigenasa 2 (COX-2), y también los medicamentos preventivos antimigrañosos, como el valproato, el topiramato y la toxina botulínica tipo A. Además, algunos compuestos que eliminan la crisis migrañosa al actuar específicamente sobre el CGRP mostraron resultados promisorios en ensayos clínicos recientes. Existen datos crecientes sobre la presencia de fenómenos inflamatorios transitorios, secundarios a la activación trigeminovascular, que comprenden el aumento temporal de algunas citoquinas proinflamatorias, moléculas de adhesión e interleuquina 8 (IL-8), el incremento del factor nuclear kappa B (NFκB) y el aumento de la sintasa de óxido nítrico inducible (iNOS). De acuerdo con estos hallazgos, los fármacos con efecto sobre la respuesta inflamatoria, que inhiban selectivamente la transcripción mediada por el NFκB o la expresión de genes proinflamatorios, representan estrategias promisorias para el tratamiento de la migraña.

Palabras clave
activación trigeminovascular, inflamación neurogénica, péptido relacionado genéticamente con la calcitonina, eventos inflamatorios mediados por el factor nuclear kB


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Abstract
Activation of the trigeminovascular system is thought to play a pivotal role in the induction and maintenance of migraine attack. Neurogenic inflammation consequent to its activation has been proposed as a central pathogenic mechanism for migraine. Calcitonin gene-related peptide (CGRP) release and nitric oxide (NO) production are the most relevant events in neurogenic inflammation underlying the headache phase of migraine. Strong evidence in animal models and clinical investigation have focused on anti-migraine compounds that limit events induced by activation of trigeminal neurons, in particular, CGRP release and meningeal vasodilation. They include effective drugs for acute migraine treatment, such as triptans, ergot derivatives, non-steroidal anti-inflammatory drugs, cyclooxygenase (COX)-2 inhibitors, and also anti-migraine preventive drugs, such as valproate, topiramate and botulinum toxin type A. Moreover, compounds that abort migraine attack by precisely targeting CGRP have recently shown promising results in clinical trials. Accumulating data support the occurrence of transitory inflammatory events consequent to trigeminovascular activation involving a transient increase of some proinflammatory cytokines, adhesion molecules and interleukin (IL)-8, the enhancement of nuclear factor kappa B (NFκB) activity and up-regulation of inducible NO synthase (iNOS). Based on these findings, drugs targeting the inflammatory response by selective inhibition of NFκB-driven transcription or downstream proinflammatory gene expression offer promising approaches to the treatment of migraine.

Key words
trigeminovascular activation, neurogenic inflammation, calcitonin gene-related peptide, nuclear factor kB mediated inflammatory events


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Clasificación en siicsalud
Artículos originales > Expertos del Mundo >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Neurología
Relacionadas: Bioquímica, Diagnóstico por Laboratorio, Medicina Interna



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Enviar correspondencia a:
Paola Sarchielli, Neurologic Clinic, Department of Medical and Surgical Specialties and Public Health, University of Perugia, Ospedale S. Maria della Misericordia, 06156, Sant'Andrea delle Fratte, Perugia, Italia
Patrocinio y reconocimiento:
A John A. Toomey, por la edición de la versión en inglés, y a Marisa M. Morson por su ayuda técnica.
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