期刊
NEUROSCIENCE LETTERS
卷 649, 期 -, 页码 116-123出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2017.04.017
关键词
Dopamine analgesia; Spinal cord; Neuropathic pain; Antidepressants; Rats
资金
- Ministry of Education, Culture, Sports, Scientific and Technology of Japan [26670678]
- Grants-in-Aid for Scientific Research [26670678] Funding Source: KAKEN
Antidepressants such as tricyclic antidepressants, and serotonin noradrenaline reuptake inhibitors are a first-line treatment for neuropathic pain. Here, we aimed to determine the involvement of the spinal dopaminergic system in the antihyperalgesic effects of antidepressants in a rat model of neuropathic pain induced by spinal nerve ligation (SNL). The right L5 spinal nerve of male Sprague-Dawley rats was ligated under inhalation anesthesia to induce hyperalgesia. Behavioral testing was performed by measuring ipsilateral hindpaw withdrawal thresholds after intraperitoneal injection of amitriptyline, duloxetine, milnacipran, and fluoxetine. D2-like receptors were blocked by intrathecal administration of sulpiride. We also determined the concentrations of dopamine in the spinal cord using microdialysis after injection of antidepressants. The dopamine contents in the spinal dorsal horn were also measured in normal and SNL rats at 2, 3, 4, and 8 weeks after SNL surgery. Intraperitoneal injection of amitriptyline, duloxetine, milnacipran, and fluoxetine (3-30 mg/kg) produced antihyperalgesic effects, and prevented by intrathecal pre-injection of sulpiride (30 mu g). Microdialysis revealed the dopamine levels in the spinal cord were increased after intraperitoneal injection of each antidepressant (10 mg/kg). Furthermore, the dopamine content in homogenized spinal cord tissue were increased at 2 weeks after SNL and then subsequently declined. Our results suggest that the effect of antidepressants against neuropathic pain is related to modulation of not only noradrenalin and serotonin but also dopamine levels in the spinal cord. (C) 2017 Elsevier B.V. All rights reserved.
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