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Los canales iónicos HCN2 juegan un papel central en el dolor inflamatorio y neuropático
Edward C Emery1, Gareth T Young, Esther M Berrocoso
1Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.
Science (New York, N.Y.)
|September 10, 2011
Resumen
El canal iónico HCN2 es crucial para iniciar el dolor neuropático al impulsar el disparo del potencial de acción en los nociceptores. La eliminación de HCN2 en neuronas específicas sensibles al dolor previene el desarrollo de dolor neuropático después de una lesión nerviosa.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Investigación del dolor Investigación del dolor.
- Fisiología del canal iónico Fisiología del canal iónico
Sus antecedentes:
- La velocidad de disparo del potencial de acción en los nociceptores determina la intensidad del dolor.
- Los canales iónicos activados por hiperpolarización de nucleótidos cíclicos (HCN), específicamente HCN2, modulan la excitabilidad neuronal al generar una corriente hacia adentro (I(h)).
- Se sabe que el monofosfato cíclico de adenosina (cAMP) regula la I(h).
Objetivo del estudio:
- Para investigar el papel de HCN2 en la función nociceptor y la percepción del dolor.
- Para determinar si las corrientes mediadas por HCN2 contribuyen al desarrollo del dolor neuropático.
Principales métodos:
- La deleción genética del HCN2 en los nociceptores que expresan Na{V}1.8 en ratones.
- Evaluación de los umbrales de dolor en condiciones normales, inflamatorias y después de la lesión nerviosa.
- Análisis electrofisiológico de I(h) y disparo del potencial de acción en los nociceptores.
Principales resultados:
- La deleción genética de HCN2 abolió el componente sensible a la cAMP de I ((h) en los nociceptores.
- El aumento de la cAMP no indujo el disparo del potencial de acción en los nociceptores que carecen de HCN2.
- Los ratones con HCN2 eliminado en los nociceptores exhibieron umbrales de dolor normales, pero carecían de hiperalgesia para calentarse durante la inflamación.
- Estos ratones no desarrollaron dolor neuropático después de la lesión nerviosa.
Conclusiones:
- La activación del potencial de acción impulsado por HCN2 en los nociceptores que expresan Na(V) 1.8 es esencial para iniciar el dolor neuropático.
- El HCN2 juega un papel crítico en el desarrollo de la hiperalgesia térmica durante la inflamación y el dolor neuropático después de una lesión nerviosa.
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