Sotgiu Maria Luisa, Valente Maurizio, Storchi Riccardo, Caramenti Giancarlo, Mario Biella Gabriele Eliseo
Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Bldg. LITA, Via Fratelli Cervi 93, Segrate (MI), Italy.
Brain Res. 2008 Jan 10;1188:69-75. doi: 10.1016/j.brainres.2007.10.030. Epub 2007 Oct 22.
We investigated in different experimental rat models the potential facilitatory contribution of the medullary dorsal reticular nucleus (DRt) descending pathway to the expressions of the sensory spinal neuron sensitization such as increased spontaneous and noxious evoked activities, responsivity to heterotopic afferences stimulation and long lasting afterdischarges (ADs). We carried out experiments by recording from ipsilateral lumbar Wide Dynamic Range (WDR) neurons and by simultaneously monitoring the DRt neuron activity in neuropathic pain rats with chronic constriction injury of one sciatic nerve (CCI), in sham-operated and in "intact" rats. In particular, we recorded the spinal neuron spontaneous activities and the activities evoked by noxious stimulations of ipsi- and contralateral sciatic supplied areas before and during DRt activity blockade. Additionally, in "intact rats" we modulated WDR activity by iontophoretic NMDA to mimic CCI WDR hyperactivity without peripheral damage. We found that during DRt activity blockade in CCI rat neurons and in "intact" rat NMDA-treated neurons, the spontaneous activity was significantly reduced, the responses to contralateral sciatic area stimulation were reduced or suppressed, the responses to ipsilateral sciatic area were poorly affected (slightly reduced or unaffected), except for the poststimulus afterdischarges that were mostly suppressed. In sham-operated rats, the neuronal activity was not affected by DRt blockade. The finding that during the DRt nucleus blockade some expressions of spinal neurons sensitization, seemingly associated to sensory disorders in neuropathic pain, fade or extinguish designates a likely facilitatory role of DRt in the maintenance of neuronal sensitization and thus a contribution to neuropathic pain state.
我们在不同的实验大鼠模型中研究了延髓背侧网状核(DRt)下行通路对感觉性脊髓神经元敏化表达的潜在促进作用,如自发活动和伤害性诱发活动增加、对异位传入刺激的反应性以及持久的后放电(ADs)。我们通过记录同侧腰段广动力范围(WDR)神经元的活动,并同时监测一侧坐骨神经慢性压迫损伤(CCI)的神经病理性疼痛大鼠、假手术大鼠和“完整”大鼠中DRt神经元的活动来进行实验。特别是,我们记录了在DRt活动阻断之前和期间脊髓神经元的自发活动以及同侧和对侧坐骨神经支配区域的伤害性刺激所诱发的活动。此外,在“完整大鼠”中,我们通过离子导入NMDA来调节WDR活动,以模拟无外周损伤的CCI大鼠WDR的活动亢进。我们发现,在CCI大鼠神经元和“完整”大鼠NMDA处理神经元的DRt活动阻断期间,自发活动显著降低,对侧坐骨神经区域刺激的反应降低或受到抑制,对同侧坐骨神经区域的反应受影响较小(略有降低或未受影响),除了刺激后的后放电大多受到抑制。在假手术大鼠中,神经元活动不受DRt阻断的影响。在DRt核阻断期间,一些看似与神经病理性疼痛中的感觉障碍相关的脊髓神经元敏化表达减弱或消失,这一发现表明DRt在维持神经元敏化中可能具有促进作用,从而对神经病理性疼痛状态有一定作用。