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

Authors

Kunie Nakajima Department of Anesthesiology, Gunma University, Graduate School of Medicine, Gunma, Japan
Hideaki Obata Department of Anesthesiology, Gunma University, Graduate School of Medicine, Gunma, Japan
Nobuhisa Iriuchijima Department of Anesthesiology, Gunma University, Graduate School of Medicine, Gunma, Japan
Shigeru Saito Department of Anesthesiology, Gunma University, Graduate School of Medicine, Gunma, Japan

DOI:

https://doi.org/10.47924/neurotarget2015260

Keywords:

antidepressants, neuropathic pain, spinal cord, noradrenaline

Abstract

Antidepressants are often used for the treatment of neuropathic pain. Clinical studies suggest that the efficacy of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors (SNRIs) for neuropathic pain is greater than that of selective 5-HT reuptake inhibitors (SSRIs). In the present study, we determined the efficacy and mechanisms involved in the antihyperalgesic effects of milnaciprán, an SNRI, compared with paroxetine, an SSRI, and maprotiline, a selective NA reuptake inhibitor, using a rat model of neuropathic pain. Male Sprague-Dawley rats underwent spinal nerve ligation (SNL), and the withdrawal threshold to paw pressure was measured. Intraperitoneal injection of milnaciprán (3–30 mg/kg) produced a dose-dependent antihyperalgesic effect. The effect was reversed by intrathecal injection of the a2-adrenoceptor antagonist idazoxan (30 lg), but not by various 5-HT receptor antagonists. Paroxetine produced an antihyperalgesic effect only at the highest dose tested (10 mg/kg). This effect was reversed by intrathecal injection of both idazoxan and ondansetron (30 lg), a 5-HT3 receptor antagonist. Maprotiline produced an antihyperalgesic effect (10 and 30 mg/kg), and the effect was reversed by intrathecal idazoxan. In microdialysis studies, NA and 5-HT concentrations in the spinal dorsal horn were increased after injection of either milnaciprán or paroxetine, and only NA was increased after maprotiline. Furthermore, the NA content in the spinal cord of SNL rats was greater than that in normal animals. These findings suggest that an increase in NA in the spinal cord plays an important role in the antihyperalgesic effects of not only NA reuptake inhibitors but also SSRIs

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