Effects of intrathecal administration of newer antidepressants on mechanical allodynia in rat models of neuropathic pain
Effects of intrathecal administration of newer antidepressants on mechanical allodynia in rat models of neuropathic pain
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DOI：
10.1016/j.neures.2008.10.002
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发表时间：
2009-01-01
影响因子：
2.9
通讯作者：
Nishimori, Toshikazu
中科院分区：
文献类型：
--
作者：
Ikeda, Tetsuya;Ishida, Yasushi;Nishimori, Toshikazu
抗抑郁药，特别是三环类抗抑郁药(TCAs)被广泛用于治疗各种类型的慢性和神经性疼痛。然而，三氯乙酸的抗伤害性作用是复杂的。因此，我们选择了两种功能较为明确的新型抗抑郁药：5-羟色胺和去甲肾上腺素再摄取抑制剂(SNRI)米那普兰，以及选择性5-羟色胺再摄取抑制剂(SSRIs)帕罗西汀和氟伏沙明。在两种神经病理性疼痛、坐骨神经慢性压迫损伤(CCI)和链脲佐菌素(STZ)诱导的糖尿病神经病变的大鼠模型上，观察了这些新型抗抑郁药鞘内注射的抗痛觉过敏性作用。用von Frey检验评价这些抗抑郁药的抗痛觉过敏作用。鞘内注射米那普兰对CCI和STZ诱导的糖尿病大鼠均有抗痛觉过敏作用，且呈剂量依赖关系。鞘内注射帕罗西汀或氟伏沙明对CCI大鼠的止痛作用不明显，而对STZ诱导的糖尿病大鼠均有剂量依赖性的止痛作用。这些结果表明，在这两种神经病理性疼痛动物模型的发展和/或维持方面存在着相当大的差异，并提示这三种抗抑郁药中的每一种都可能对治疗糖尿病神经病理性疼痛有效。(C)2008年爱思唯尔爱尔兰有限公司和日本神经科学学会。版权所有。
Antidepressants, especially tricyclic antidepressants (TCAs) are widely used for the treatment of various types of chronic and neuropathic pain. The antinociceptive effects of TCAs are, however, complicated. Therefore, two kinds of newer antidepressants whose functions have been more fully clarified were selected, milnacipran, a serotonin and noradrenaline reuptake inhibitor (SNRI) and paroxetine and fluvoxamine, which are selective serotonin reuptake inhibitors (SSRIs). The antiallodynic effects of intrathecal administration of these newer antidepressants were examined in two rat models of neuropathic pain, chronic constriction injury (CCI) of the sciatic nerve and streptozotocin (STZ)-induced diabetic neuropathy. The antiallodynic effect of these antidepressants was evaluated using the von Frey test. The intrathecal administration of milnacipran had an antiallodynic effect in both CCI and STZ-induced diabetic rats in a dose-dependent manner. On the other hand, the intrathecal administration of either paroxetine or fluvoxamine elicited little antiallodynic effect in CCI rats, while both SSRIs had antiallodynic effects in the STZ-induced diabetic rats in a dose-dependent manner. These results indicate a considerable difference to exist in the development and/or maintenance between these two animal models of neuropathic pain and suggest that each of these three antidepressants may be effective for the treatment of diabetic neuropathic pain. (C) 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.