Department of Anesthesiology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Neurosci Lett. 2010 Sep 6;481(2):102-4. doi: 10.1016/j.neulet.2010.06.061. Epub 2010 Jun 25.
Neuropathic pain models are classified as central and peripheral pain models. Although various peripheral neuropathic pain models are established, central pain models are based only on spinal cord injury. DSP-4 is a competitive inhibitor of norepinephrine uptake that selectively degenerates the locus coeruleus (LC)-noradrenergic neurons projection to the cerebral cortex and hippocampus. In the present study, we have tested whether lesion of LC-noradrenergic neurons by ip DSP-4 (0, 10, 30, 50 mg/kg, n=7 each) could provide a new central neuropathic pain model in rats using a hot-plate and tail-flick tests. DSP-4 significantly reduced the hot-plate latency and norepinephrine contents especially in the coerulean regions. However, DSP-4 did not change tail-flick latency. There are significant correlations of the latency in the hot-plate test with norepinephrine contents in the cerebral cortex (r=0.432, p=0.022), the hippocampus (r=0.465, p=0.013) and the pons (r=0.400, p=0.035) but not with those in the hypothalamus and the spinal cord. As response to hot-plate and tail-flick implies supra-spinal process and spinal reflex, respectively, central neuropathic pain may be facilitated by DSP-4 depleting LC-noradrenergic neurons although the present data are preliminary.
神经病理性疼痛模型分为中枢性和周围性疼痛模型。尽管已经建立了各种周围性神经病理性疼痛模型，但中枢性疼痛模型仅基于脊髓损伤。DSP-4 是去甲肾上腺素摄取的竞争性抑制剂，可选择性地使蓝斑（LC）-去甲肾上腺素能神经元投射到大脑皮层和海马体退化。在本研究中，我们使用热板和尾巴闪烁测试测试了腹腔注射 DSP-4（0、10、30、50mg/kg，每组 7 只）是否会导致 LC-去甲肾上腺素能神经元损伤，从而在大鼠中建立新的中枢性神经病理性疼痛模型。DSP-4 显著降低了热板潜伏期和去甲肾上腺素含量，尤其是在蓝斑区域。然而，DSP-4 并没有改变尾巴闪烁潜伏期。热板测试的潜伏期与大脑皮层（r=0.432，p=0.022）、海马体（r=0.465，p=0.013）和桥脑（r=0.400，p=0.035）中的去甲肾上腺素含量呈显著相关性，但与下丘脑和脊髓中的去甲肾上腺素含量无相关性。由于热板和尾巴闪烁测试分别反映了脊髓上和脊髓反射过程，因此尽管目前的数据尚属初步，但 DSP-4 耗尽 LC-去甲肾上腺素能神经元可能会促进中枢性神经病理性疼痛。
