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Identificación de las vías requeridas para afrontar los comportamientos asociados con el dolor sostenido
Tianwen Huang1,2, Shing-Hong Lin1,2, Nathalie M Malewicz3
1Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Nature
|December 12, 2018
Resumen
Los investigadores identificaron neuronas espinales específicas que controlan las conductas de afrontamiento del dolor, como lamer heridas, en ratones. Este descubrimiento arroja luz sobre la base neuronal de las respuestas al dolor sostenido y desafía cómo medimos el dolor.
Área de la Ciencia:
- La neurociencia
- Investigación del dolor
- Sistema somatosensorial
Sus antecedentes:
- Los estímulos nocivos provocan respuestas reflexivas y de afrontamiento distintas en animales y humanos.
- Los circuitos neuronales subyacentes a estas respuestas duales al dolor no se comprenden completamente.
- Comprender estos circuitos es crucial para el manejo del dolor y la investigación.
Objetivo del estudio:
- Para identificar los circuitos neuronales espinales específicos responsables de las conductas de afrontamiento del dolor.
- Investigar el papel de las neuronas espinales que expresan TAC1 en la mediación de las respuestas al dolor sostenido.
- Explorar la relación entre los circuitos espinales y los núcleos tálamicos mediales en el procesamiento del dolor.
Principales métodos:
- Utilizó herramientas genéticas (TAC1Cre y LBX1Flpo) para atacar y eliminar neuronas espinales específicas en ratones.
- Respuestas de comportamiento evaluadas a estímulos nocivos, incluyendo lamer, aversión y retiro reflexivo.
- Proyecciones neuronales investigadas desde la médula espinal hasta los núcleos tálamicos y parabraquiales.
- Se examinaron las funciones de las neuronas sensoriales primarias específicas (MRGPRD y TRPV1) en respuestas distintas al dolor.
Principales resultados:
- La ablación de las neuronas espinales que coexpresan TAC1 y LBX1 abolió el lamido persistente y la aversión condicionada a los estímulos de dolor sostenidos.
- Estas neuronas espinales específicas se proyectan a los núcleos tálamicos mediales, directa e indirectamente.
- Las respuestas defensivas reflexivas permanecieron intactas después de la ablación, lo que indica un papel selectivo en el afrontamiento.
- Las neuronas sensoriales primarias (MRGPRD y TRPV1) muestran segregación funcional para comportamientos reflexivos versus de afrontamiento del dolor.
Conclusiones:
- Las neuronas espinales que coexpresan TAC1 y LBX1 son impulsores críticos de las conductas de afrontamiento del dolor.
- Una vía neural distinta que involucra a las neuronas del linaje TAC1 espinal y el tálamo medial media las respuestas de dolor sostenido.
- Los hallazgos revelan una subdivisión fundamental en el sistema somatosensorial para diferentes comportamientos de dolor.
- Los métodos actuales que se basan únicamente en respuestas reflexivas pueden no capturar completamente la experiencia del dolor sostenido.
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