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延髓脊髓去甲肾上腺素能通路的损伤会阻断地昔帕明对大鼠C纤维诱发的伤害性反射的抑制作用。

Lesion of the bulbospinal noradrenergic pathways blocks desipramine-induced inhibition of the C-fiber evoked nociceptive reflex in rats.

作者信息

Hernández A, Laurido C, Mondaca M, Pelissier T, Burgos H, Soto-Moyano R

机构信息

Departamento de Ciencias Biológicas, Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, Correo 33, Santiago, Chile.

出版信息

Neurosci Lett. 2001 Apr 13;302(1):1-4. doi: 10.1016/s0304-3940(01)01544-0.

DOI:10.1016/s0304-3940(01)01544-0
PMID:11278097
Abstract

Desipramine-induced inhibition of spinal cord nociceptive transmission was studied in rats with or without lesion of the bulbospinal noradrenergic system by recording the C-fiber evoked nociceptive reflex from a hind limb. Bulbospinal noradrenergic projections were lesioned by injecting intrathecally 20 microg of 6-hydroxydopamine 2 weeks before the electrophysiological experiments. Results show that desipramine (5, 10 and 20 mg/kg intraperitoneally) produced dose-dependent inhibition of the C reflex response duration in rats having intact noradrenergic bulbospinal systems. The inhibitory effect of desipramine was reduced or even abolished in rats pre-treated with 6-hydroxydopamine. In addition, [3H]-noradrenaline uptake was significantly lower in spinal cord slices arising from 6-hydroxydopamine lesioned animals, as compared to that from intact rats. These observations support the notion that the antinociceptive activity of antidepressants with noradrenergic selectivity depends on a normal rate of endogenous noradrenaline released by bulbospinal neurons.

摘要

通过记录后肢C纤维诱发的伤害性反射,研究了地昔帕明对有或无延髓脊髓去甲肾上腺素能系统损伤的大鼠脊髓伤害性传递的抑制作用。在电生理实验前2周,通过鞘内注射20微克6-羟基多巴胺来损伤延髓脊髓去甲肾上腺素能投射。结果表明,地昔帕明(腹腔注射5、10和20毫克/千克)对去甲肾上腺素能延髓脊髓系统完整的大鼠的C反射反应持续时间产生剂量依赖性抑制。在用6-羟基多巴胺预处理的大鼠中,地昔帕明的抑制作用减弱甚至消失。此外,与完整大鼠相比,6-羟基多巴胺损伤动物的脊髓切片中[3H]-去甲肾上腺素摄取显著降低。这些观察结果支持了这样一种观点,即具有去甲肾上腺素能选择性的抗抑郁药的抗伤害感受活性取决于延髓脊髓神经元释放内源性去甲肾上腺素的正常速率。

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