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Regulación del receptor NMDA de la liberación de la sustancia P de los nociceptores aferentes primarios
H Liu1, P W Mantyh, A I Basbaum
1Department of Anatomy, University of California San Francisco, 94143, USA.
Nature
|April 17, 1997
Resumen
La activación de los receptores de N-metil-D-aspartato (NMDA) en la médula espinal libera la sustancia P, causando dolor persistente y cambios estructurales. El bloqueo de los receptores o vías de la sustancia P reduce estos efectos, lo que sugiere nuevos objetivos de tratamiento del dolor.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Investigación del dolor Investigación del dolor.
- Lesión de la médula espinal lesión de la médula espinal.
Sus antecedentes:
- Una lesión grave causa hiperexcitabilidad de las neuronas del cuerno dorsal, lo que lleva a dolor crónico, hiperalgesia y alodinia.
- Los receptores de glutamato tipo N-metil-D-aspartato (NMDA) median estos cambios de dolor en la médula espinal.
Objetivo del estudio:
- Investigar el papel de la activación del receptor NMDA en la señalización del dolor y los cambios neuronales de la médula espinal.
- Para explorar la participación de la sustancia P en el dolor mediado por el receptor NMDA.
Principales métodos:
- Inyección de NMDA en el líquido cefalorraquídeo de la médula espinal de la rata.
- Administración de sustancias antagonistas de los receptores P.
- Eliminación de las fibras que contienen sustancia P utilizando capsaicina.
Principales resultados:
- La activación de NMDA indujo dolor, liberación de sustancia P e internalización del receptor en las neuronas del cuerno dorsal.
- Se observaron cambios dendríticos estructurales en las neuronas del cuerno dorsal.
- Los antagonistas de la sustancia P y la capsaicina redujeron significativamente el dolor y las alteraciones morfológicas inducidas por el NMDA.
Conclusiones:
- Los receptores presinápticos de NMDA en las fibras del dolor facilitan la transmisión nociceptiva a través de la sustancia P y la liberación de glutamato.
- Dirigirse a los receptores presinápticos NMDA ofrece una estrategia terapéutica potencial para el dolor persistente provocado por una lesión.
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