Lin Q, Wu J, Peng Y B, Cui M, Willis W D
Department of Anatomy and Neurosciences, Marine Biomedical Institute, The University of Texas Medical Branch, Galveston, Texas 77555-1069, USA.
J Neurophysiol. 1999 Mar;81(3):1086-94. doi: 10.1152/jn.1999.81.3.1086.
This study concentrated on whether an increase in spinal nitric oxide (NO) diminishes inhibition of spinothalamic tract (STT) cells induced by activating the periaqueductal gray (PAG) or spinal glycinergic and GABAergic receptors, thus contributing to the sensitization of STT neurons. A reduction in inhibition of the responses to cutaneous mechanical stimuli induced by PAG stimulation was seen in wide dynamic range (WDR) STT cells located in the deep layers of the dorsal horn when these neurons were sensitized during administration of a NO donor, 3-morpholinosydnonimine (SIN-1), into the dorsal horn by microdialysis. In contrast, PAG-induced inhibition of the responses of high-threshold (HT) and superficial WDR STT cells was not significantly changed by spinal infusion of SIN-1. A reduction in PAG inhibition when STT cells were sensitized after intradermal injection of capsaicin could be nearly completely blocked by pretreatment of the dorsal horn with a NO synthase inhibitor, 7-nitroindazole. Moreover, spinal inhibition of nociceptive activity of deep WDR STT neurons elicited by iontophoretic release of glycine and GABA agonists was attenuated by administration of SIN-1. This change paralleled the change in PAG-induced inhibition. However, the inhibition of HT and superficial WDR cells induced by glycine and GABA release did not show a significant change when SIN-1 was administered spinally. Combined with our recent results, these data show that the effectiveness of spinal inhibition can be reduced by the NO/cGMP pathway. Thus disinhibition may constitute one mechanism underlying central sensitization.
本研究聚焦于脊髓一氧化氮（NO）的增加是否会减弱通过激活中脑导水管周围灰质（PAG）或脊髓甘氨酸能及γ-氨基丁酸能（GABA能）受体所诱导的脊髓丘脑束（STT）细胞的抑制作用，进而导致STT神经元的敏化。当通过微透析将NO供体3-吗啉代辛二亚胺（SIN-1）注入背角使这些神经元敏化时，在位于背角深层的广动力范围（WDR）STT细胞中，观察到PAG刺激所诱导的对皮肤机械刺激反应的抑制作用减弱。相比之下，脊髓内注入SIN-1并未显著改变PAG对高阈值（HT）和浅层WDR STT细胞反应的抑制作用。皮内注射辣椒素使STT细胞敏化后，PAG抑制作用的减弱几乎可被用一氧化氮合酶抑制剂7-硝基吲唑预处理背角完全阻断。此外，给予SIN-1可减弱脊髓对离子导入释放甘氨酸和GABA激动剂所引发的深层WDR STT神经元伤害性活动的抑制作用。这一变化与PAG诱导的抑制作用变化平行。然而，脊髓给予SIN-1时，甘氨酸和GABA释放所诱导的对HT和浅层WDR细胞的抑制作用未显示出显著变化。结合我们最近的研究结果，这些数据表明NO/cGMP途径可降低脊髓抑制的有效性。因此，去抑制可能是中枢敏化的一种潜在机制。
