REVISTA

Reducción de la eficacia analgésica de la gabapentina en el dolor neuropático crónico

Valoración Valoración: 3 Estrellas

Descripción: El efecto analgésico de la gabapentina parece estar reducido en dolor neuropático crónico. Sin embargo, puede disminuirse este efecto por medio de valproato según este estudio

TITULO FUENTE ORIGINAL:

Gabapentin loses efficacy over time after nerve injury in rats: role of glutamate transporter-1 in the locus coeruleus

AUTORES:

Kimura M, Eisenach JC, Hayashida K.

REVISTA ABREV.:

Pain

AÑO:

2016

REFERENCIA:

157(9):2024-32

DOI:

10.1097/j.pain.0000000000000608

RESUMEN ORIGINAL:

Despite being one of the first-choice analgesics for chronic neuropathic pain, gabapentin sometimes fails to provide analgesia, but the mechanisms for this lack of efficacy is unclear. Rats with nerve injury including L5-L6 spinal nerve ligation (SNL) respond uniformly and well to gabapentin, but many of these studies are performed within just a few weeks of injury, questioning their relevance... + Leer más

Despite being one of the first-choice analgesics for chronic neuropathic pain, gabapentin sometimes fails to provide analgesia, but the mechanisms for this lack of efficacy is unclear. Rats with nerve injury including L5-L6 spinal nerve ligation (SNL) respond uniformly and well to gabapentin, but many of these studies are performed within just a few weeks of injury, questioning their relevance to chronic neuropathic pain. In this study, intraperitoneal gabapentin showed a time-dependently reduction in antihypersensitivity after SNL, associated with downregulation of astroglial glutamate transporter-1 (GLT-1) in the locus coeruleus (LC). Consistently, SNL also time-dependently increased basal but masked gabapentin-induced noradrenergic neuronal activity in the LC. In rats 2 weeks after SNL, knock-down of GLT-1 in the LC reduced the antihypersensitivity effect of gabapentin. In rats 8 weeks after SNL, increasing GLT-1 expression by histone deacetylase inhibitor valproate restored the antihypersensitivity effect of gabapentin, associated with restored gabapentin-induced noradrenergic neuronal activity in the LC and subsequent spinal noradrenaline release. Knock-down of GLT-1 in the LC reversed the effect of valproate to restore gabapentin-induced antihypersensitivity. In addition, the antihypersensitivity effect of the intrathecal α2-adrenoceptor agonist clonidine also decreased with time after SNL injury. These results suggest that downregulation of GLT-1 in the LC and reduced spinal noradrenergic inhibition contribute to impaired analgesic efficacy from gabapentin in chronic neuropathic pain and that valproate can rescue this impaired efficacy.

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