Role of prostaglandins and nitric oxide in the spinal plasticity

本研究旨在探讨前列腺素(PG)2αGT；对大鼠脊髓可塑性的影响。为了观察鞘内注射前列腺素F_2α和前列腺素F_2对不同类型感觉加工的影响，采用甩尾(TE)试验和结肠扩张(CD)试验测定了大鼠对伤害性刺激的反应，以及对机械压力(SWM)产生的戒断反应。给予PGF_2α和GT后，Tf潜伏期和CD阈值略有下降；用一氧化氮合酶抑制剂L-精氨酸后处理可逆转上述下降。SWM产生的激越评分(ASS)在P0给药后明显升高，且持续7d。在治疗后的前60 mm，用L-NMMA、NMDA拮抗剂MK-801和GABA激动剂巴氯芬使ASS降低。在随后的7d内，L-NMMA和巴氯芬预处理可抑制ASS的增加。经前列腺素F_2α和前列腺素F_2α和前列腺素T_2治疗后，一氧化氮合酶免疫反应阳性神经元的数量增加，尤以III、V板层较生理盐水处理组增加明显。用电生理学方法检测PGF_2α&gt；诱发的脊髓神经元电活动的变化。前列腺素F_2增加自发活动。经PGF2a处理后，脊髓背角神经元的感受野面积(RF)呈剂量依赖性增加，经L-NMMA处理后，RF增大的幅度减小。这些结果表明，脊髓背角神经元的过度活动在脊髓水平的感觉加工通路中起着重要的触发超敏状态的作用，一氧化氮系统包括GABA和NMDA受体系统可能参与了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.