Role of prostaglandins and nitric oxide in the spinal plasticity

本实验旨在探讨前列腺素（PG） _<2 α >对大鼠脊柱可塑性的影响。为了研究鞘内注射PGF_<2 α >对大鼠不同类型感觉加工的影响，采用甩尾（TE）试验和结肠膨胀（CD）试验测量大鼠对有害刺激的反应，并测量semms - weinstein -丝（SWM）产生的机械压力的戒断反应。在给予PGF_<2 α bb0后，TF潜伏期和CD阈值略有下降，但在给予一氧化氮合酶（NOS）抑制剂ng - monomethyi - l -精氨酸（L-NMMA）后，这种下降趋势被逆转。给药后SWM的躁动评分（ASs）升高，且持续7 d。L-NMMA、NMDA拮抗剂MK-801和GABA激动剂巴氯芬治疗后，前60 mm的ASs下降。在随后的7天内，L-NMMA和巴氯芬预处理抑制了ASs的增加。与生理盐水处理相比，PGF_<2 α >处理后NOS-免疫反应神经元数量增加，尤以III和V层增加。采用电生理方法观察PGF_<2 α >引起的脊髓神经元电活动变化。PGF_2增加自发活性。大鼠脊髓背角神经元的感受野面积（RF）在PGF_2 a治疗后呈剂量依赖性增加。经L-NMMA处理后，增大的RF减小。这些结果提示，脊髓背角神经元的过度活跃在脊髓水平感觉加工通路的超敏状态触发中起重要作用，包括GABA和NMDA受体系统在内的一氧化氮系统可能参与了α诱导的超敏状态的启动和维持。

This study was designed to investigate the role of prostaglandin (PG) _<2 alpha> on the spinal plasticity in rats. To examine the effects of intrathecally administered PGF_<2 alpha> on the different types of sensory processing, the tail flick (TE) test and the colorectal distension (CD) test were employed to measure responses to noxious stimuli, and the withdrawal response to mechanical pressure produced by Semmes-Weinstein-filaments (SWM) was measured. TF latencies and CD thresholds slightly decreased following the administration of PGF_<2 alpha> Those decreases were reversed by the posttreatment with nitric oxide synthase (NOS) inhibitor, NG-monomethyI-L-arginine (L-NMMA). Agitation scores (ASs) produced by SWM were increased after administration of P0, and the increase in ASs lasted for 7 days. Posttreatment with L-NMMA, NMDA antagonist, MK-801, and GABA agonist, baclofen, decreased in ASs for the first 60 mm. Pretreatment with L-NMMA and baclofen inhibited the increase in ASs during the subsequent 7 days. The number of NOS- immunoreactive neurons after the treatment with PGF_<2 alpha> was increased, especially in lamina III and V compared with saline treatment. Electrophysiological studies were used to examine PGF_<2 alpha> evoked changes in electrical activity of spinal cord neurons. PGF_2 increased spontaneous activity. Receptive field areas (RF) in spinal dorsal horn neurons increased dose-dependently following the treatment with PGF_2 a .The enlarged RF was reduced by the treatment with L-NMMA.These results suggest that hyperactivity of spinal dorsal horn neurons plays an important role in trigger a hypersensitive state in sensory processing pathways at the spinal level and that nitric oxide system including GABA and NMDA receptor systems may be involved the initiation and the maintenance of alpha induced hypersensitive state.