Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
Neurosci Lett. 2011 Sep 26;503(1):20-2. doi: 10.1016/j.neulet.2011.07.056. Epub 2011 Aug 6.
Neurotropin is a nonprotein extract isolated from inflamed skin of rabbits inoculated with vaccinia virus, and used for treatment of neuropathic pain. In the present study, we have determined whether neurotropin could exert antinociceptive action using the central neuropathic pain model that we recently established. Rats were randomly allocated to 3 groups: Sham group (n=20), DSP-4 [N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine] group (50mg/kg ip, n=18), and DSP-4+5,7-DHT [5,7-dihydroxytryptamine] group (ip DSP-4 50mg/kg+icv 5,7-DHT 200μg, n=18). In Sham, DSP-4 and DSP-4+5,7-DHT groups, the effects of ip neurotropin (100NU/Kg) on hot-plate latency in rats with no lesion, noradrenergic neuron depletion and both noradrenergic and serotonergic neuronal depletion were studied, respectively. Rats in each group were subdivided equally to 2 subgroups: saline and neurotropin. After completion of the hot-plate tests, each rat was decapitated, the cerebral cortex was dissected from its internal structure for measurement of norepinephrine contents. Hot-plate latency significantly decreased by ∼40% 10 days after ip DSP-4 or after ip DSP-4 and 5,7-DHT. Norepinephrine contents in DSP-4 treated rats (55.6±6.3ng/ng tissue) and DSP-4+5,7-DHT treated rats (35.3±6.3ng/ng tissue) were significantly lower than those in intact rats (131.6±5.7ng/ng tissue, p<0.01). Neurotropin significantly increased the area under the curve (AUC) of the hot-plate latency in the DSP-4 and DSP-4+5,7-DHT groups but not in the Sham group. There was a significant correlation between AUC and norepinephrine contents in saline subgroup (p<0.01, r=0.597) but not in neurotropin subgroup in DSP-4 group. Neurotropin exerted an antinociceptive effect in DSP-4 induced central neuropathic pain. The present data suggest neuronal pathways other than descending inhibitory noradrenergic and serotonergic systems may be involved in neurotropin mediated antinociception.
神经妥乐平是一种从接种牛痘病毒的兔炎性皮肤中分离出来的非蛋白提取物，用于治疗神经性疼痛。在本研究中，我们使用我们最近建立的中枢神经性疼痛模型，确定神经妥乐平是否具有镇痛作用。大鼠随机分为 3 组：假手术组（n=20）、DSP-4[N-（-2-氯乙基）-N-乙基-2-溴苯甲胺]组（50mg/kg，ip，n=18）和 DSP-4+5,7-DHT[5,7-二羟基色胺]组（ip DSP-4 50mg/kg+icv 5,7-DHT200μg，n=18）。在假手术组、DSP-4 组和 DSP-4+5,7-DHT 组中，分别研究了 ip 神经妥乐平（100NU/Kg）对无损伤、去甲肾上腺素能神经元耗竭以及去甲肾上腺素能和 5-羟色胺能神经元耗竭大鼠的热板潜伏期的影响。每组大鼠均等分为 2 个亚组：生理盐水和神经妥乐平。完成热板试验后，断头处死大鼠，从其内部结构中分离出大脑皮层，测量去甲肾上腺素含量。ip DSP-4 或 ip DSP-4 加 5,7-DHT 后 10 天，热板潜伏期显著降低约 40%。DSP-4 处理大鼠（55.6±6.3ng/ng 组织）和 DSP-4+5,7-DHT 处理大鼠（35.3±6.3ng/ng 组织）的去甲肾上腺素含量明显低于完整大鼠（131.6±5.7ng/ng 组织，p<0.01）。神经妥乐平显著增加了 DSP-4 组和 DSP-4+5,7-DHT 组的热板潜伏期曲线下面积（AUC），但在假手术组中没有。在 DSP-4 组的生理盐水亚组中，AUC 与去甲肾上腺素含量之间存在显著相关性（p<0.01，r=0.597），但在神经妥乐平亚组中没有。神经妥乐平在 DSP-4 诱导的中枢神经性疼痛中具有镇痛作用。本研究数据表明，除下行抑制性去甲肾上腺素能和 5-羟色胺能系统外，其他神经元通路可能参与了神经妥乐平介导的镇痛作用。
