Lei Jing, Ye Gang, Pertovaara Antti, You Hao-Jun
Center for Translational Medicine Research on Sensory-Motor Diseases, Yan'an University, Yan'an 716000, PR China; Department of Physiology, Faculty of Medicine, University of Helsinki, POB 63, Helsinki 00014, Finland.
Department of Rehabilitation, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China.
Neuroscience. 2020 Aug 1;440:249-266. doi: 10.1016/j.neuroscience.2020.05.043. Epub 2020 Jun 3.
Here we investigated variations of endogenous descending modulation of nociception and therapeutic effects of intramuscular (i.m.) heating-needle stimulation in early stage of Parkinson's disease (PD) induced by unilateral microinjection of 3.5 μl of 2.5 μg/μl 6-hydroxydopamine into the rat striatum. Paw withdrawal reflexes to noxious mechanical and heat stimuli in PD rats with and without exposure to i.m. 5.8% saline induced muscle nociception were evaluated. Experimental PD had no influence on mechanical or heat sensitivity in the baseline condition, whereas descending facilitation was stronger and descending inhibition was weaker in PD rats than vehicle-treated or naive rats during muscle nociception (P < 0.05). Striatal administration of 5 μg of dopamine failed to reverse the PD-associated changes in descending facilitation or inhibition, whereas dopamine in the thalamic mediodorsal (MD) nucleus and ventromedial (VM) nucleus significantly decreased the increase in descending facilitation and reversed the attenuation in descending inhibition, respectively (P < 0.05). I.m. 43 °C of heating-needle stimulation had no effects on the enhanced descending facilitation in PD rats, but it markedly increased descending inhibition and reversed the increase in the number of apomorphine-induced body rotations (P < 0.05), which effects were dose-dependently attenuated by raclopride, a dopamine 2 receptor antagonist, in the thalamic VM nucleus (P < 0.05). The results indicate that the early-stage PD is associated with enhanced descending facilitation and weakened descending inhibition. From clinical perspective, 43 °C heat therapeutic regime promises to selectively enhance descending inhibition that is accompanied by improvement of motor dysfunction in PD.
在此，我们研究了单侧向大鼠纹状体内微量注射3.5 μl 2.5 μg/μl 6-羟基多巴胺诱导帕金森病（PD）早期伤害性感受的内源性下行调制变化及肌肉注射（i.m.）热针刺激的治疗效果。评估了有无暴露于i.m. 5.8%盐水诱导的肌肉伤害性感受的PD大鼠对有害机械和热刺激的爪退缩反射。实验性PD在基线条件下对机械或热敏感性无影响，而在肌肉伤害性感受期间，PD大鼠的下行易化更强，下行抑制比溶剂处理组或正常大鼠更弱（P<0.05）。纹状体内给予5 μg多巴胺未能逆转与PD相关的下行易化或抑制变化，而丘脑背内侧（MD）核和腹内侧（VM）核中的多巴胺分别显著降低了下行易化的增加并逆转了下行抑制的减弱（P<0.05）。i.m. 43°C的热针刺激对PD大鼠增强的下行易化无影响，但它显著增加了下行抑制并逆转了阿扑吗啡诱导的身体旋转次数的增加（P<0.05），在丘脑VM核中，多巴胺2受体拮抗剂雷氯必利剂量依赖性地减弱了这些作用（P<0.05）。结果表明，PD早期与下行易化增强和下行抑制减弱有关。从临床角度来看，43°C热疗方案有望选择性增强下行抑制，同时改善PD患者的运动功能障碍。
