Time-dependent descending facilitation from the rostral ventromedial medulla maintains, but does not initiate, neuropathic pain
Time-dependent descending facilitation from the rostral ventromedial medulla maintains, but does not initiate, neuropathic pain
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DOI：
10.1523/jneurosci.22-12-05129.2002
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发表时间：
2002-06-15
影响因子：
5.3
通讯作者：
Porreca, F
中科院分区：
文献类型：
--
作者：
Burgess, SE;Gardell, LR;Porreca, F
虽然损伤引起的传入放电随着时间的推移显着下降，实验性神经性疼痛持续很长一段时间不变。这些观察结果表明，启动实验性神经性疼痛的过程可能与维持这种疼痛的过程不同。在这里，下行易化所产生的发展可塑性在延髓头端腹内侧（RVM）的启动和维持实验性神经病理性疼痛的作用进行了探讨。采用脊神经结扎法（SNL）诱导大鼠触觉和热过敏。RVM利多卡因在SNL后第6-12天阻断SNL诱导的触觉和热超敏反应，但在SNL后第3天未阻断。用皮吗啡-皂草素损伤表达μ-阿片受体的RVM细胞并不能阻止SNL诱导的触觉和热超敏反应的发生，但这些体征在SNL后第4天开始逆转至基线水平。同样，背外侧索（DLF）的病变并不能阻止SNL诱导的触觉和热超敏反应的发生，但这些体征在SNL后第4天开始逆转至基线水平。DLF的损伤也阻断了SNL诱导的脊髓强啡肽含量的增加，这被认为是促进神经病理性疼痛。这些数据区分了启动神经病理状态的机制，独立于下行的脊髓上影响和需要脊髓上促进来维持这种疼痛的其他机制。此外，这些数据表明，这些时间依赖性下降的影响可以在一些SNL诱导的可塑性在脊髓水平的基础。这种时间依赖性的下降影响驱动相关的脊髓变化，如强啡肽的上调，是维持，但不是启动，神经病理状态的关键因素。
Although injury-induced afferent discharge declines significantly over time, experimental neuropathic pain persists unchanged for long periods. These observations suggest that processes that initiate experimental neuropathic pain may differ from those that maintain such pain. Here, the role of descending facilitation arising from developing plasticity in the rostral ventromedial medulla (RVM) in the initiation and maintenance of experimental neuropathic pain was explored. Tactile and thermal hypersensitivity were induced in rats by spinal nerve ligation (SNL). RVM lidocaine blocked SNL-induced tactile and thermal hypersensitivity on post-SNL days 6-12 but not on post-SNL day 3. Lesion of RVM cells expressing mu-opioid receptors with dermorphin-saporin did not prevent the onset of SNL-induced tactile and thermal hypersensitivity, but these signs reversed to baseline levels beginning on post-SNL day 4. Similarly, lesions of the dorsolateral funiculus (DLF) did not prevent the onset of SNL-induced tactile and thermal hypersensitivity, but these signs reversed to baseline levels beginning on post-SNL day 4. Lesions of the DLF also blocked the SNL-induced increase in spinal dynorphin content, which has been suggested to promote neuropathic pain. These data distinguish mechanisms that initiate the neuropathic state as independent of descending supraspinal influences and additional mechanism(s) that require supraspinal facilitation to maintain such pain. In addition, the data indicate that these time-dependent descending influences can underlie some of the SNL-induced plasticity at the spinal level. Such time-dependent descending influences driving associated spinal changes, such as the upregulation of dynorphin, are key elements in the maintenance, but not initiation, of neuropathic states.