El aumento en la noradrenalina espinal como mayor contribuyente al efecto antihiperalgésico de antidepresivos luego de la lesión de nervio periférico en la rata: Artículo publicado originalmente en la Revista PAIN 153 (2012) 990–997

Kunie Nakajima; Hideaki Obata; Nobuhisa Iriuchijima; Shigeru Saito

doi:10.47924/neurotarget2015260

Autores/as

Kunie Nakajima Departamento de Anestesiología, Universidad de Gunma, Escuela de Graduados de Medicina, Gunma, Japón
Hideaki Obata Departamento de Anestesiología, Universidad de Gunma, Escuela de Graduados de Medicina, Gunma, Japón
Nobuhisa Iriuchijima Departamento de Anestesiología, Universidad de Gunma, Escuela de Graduados de Medicina, Gunma, Japón
Shigeru Saito Departamento de Anestesiología, Universidad de Gunma, Escuela de Graduados de Medicina, Gunma, Japón

DOI:

https://doi.org/10.47924/neurotarget2015260

Palabras clave:

antidepresivos, dolor neuropático, médula espinal, noradrenalina

Resumen

Los antidepresivos a menudo son utilizados para el tratamiento del dolor neuropático. Los estudios clínicos sugieren que la eficacia de los inhibidores de la recaptación de serotonina (5-HT) y noradrenalina (NA) (IRSN) para el dolor neuropático es mayor que aquella de los inhibidores selectivos de la recaptación de serotonina (ISRS).
En el presente estudio, determinamos la eficacia y los mecanismos involucrados en los efectos antihiperalgésicos del milnaciprán, un IRSN, comparado con paroxetina, un ISRS, y maprotilina, un inhibidor selectivo de la recaptación de la NA, utilizando un modelo de rata de dolor neuropático. Las ratas machos de tipo Sprague-Dawley fueron sometidas a ligadura del nervio espinal (LNE), y se midió el umbral de retirada a la presión de la pata. La inyección de milnaciprán (3-30 mg/kg) produjo un efecto antihiperalgésico dosis-dependiente. Dicho efecto se revirtió mediante la inyección intratecal del antagonista del adrenoreceptor a2, idazoxan (30 lg), pero no mediante antagonistas del receptor de 5-HT. La paroxetina produjo un efecto antihiperalgésico solo a la dosis máxima probada (10 mg/kg). Este efecto fue revertido por la inyección intratecal tanto de idazoxan como de ondansetrón (30 lg), un antagonista del receptor 5-HT3. La maprotilina produjo un efecto antihiperalgésico (10 y 30 mg/kg), y este efecto fue revertido por idazoxan intratecal. En estudios de microdiálisis, las concentraciones de NA y 5-HT en el asta dorsal espinal, se incrementaron después de la inyección de milnaciprán o paroxetina, indistintamente, y sólo la NA se incrementó luego de la inyección de maprotilina. Además, el contenido de NA en la médula espinal de ratas con LNE fue mayor que en los animales normales. Estos hallazgos sugieren que el incremento de NA en la médula espinal juega un papel importante en los efectos antihiperalgésicos de no solamente los inhibidores de la recaptación de NA, sino también de los ISRS.

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