Effects of Heating-needle Stimulation in Restoration of Weakened Descending Inhibition of Nociception in a Rat Model of Parkinson's Disease
Effects of Heating-needle Stimulation in Restoration of Weakened Descending Inhibition of Nociception in a Rat Model of Parkinson's Disease
复制标题
热针刺激对帕金森病大鼠模型伤害感受下行抑制减弱恢复的影响
DOI：
10.1016/j.neuroscience.2020.05.043
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发表时间：
2020
期刊：
影响因子：
3.3
通讯作者：
Hao-Jun You
中科院分区：
文献类型：
--
作者：
Jing Lei;Gang Ye;Antti Pertovaara;Hao-Jun You
在这里，我们研究了内源性伤害性下行调制的变化和肌肉注射(IM)的治疗效果。单侧纹状体内微量注射3.5 μL 2.5 μg/μL 6-羟基多巴胺诱发早期帕金森病。帕金森病大鼠接受和不接受肌肉注射时对机械和热刺激的缩爪反应。测定5.8%生理盐水诱导的肌肉伤害性反应。在基础状态下，实验性帕金森病对机械敏感性和热敏感性无明显影响，但在肌肉伤害性反应中，帕金森病大鼠的下行促进作用强于赋形剂治疗组和幼稚大鼠，下行抑制作用弱于单纯帕金森病大鼠(P<； 0.05)。纹状体注射5 μg多巴胺不能逆转帕金森病引起的下行易化或抑制的改变，而丘脑内侧背核(MD)和腹内侧核(Vm)的多巴胺分别显著降低帕金森病所致的下行易化和抑制减弱(P<； 0.0 5)。I.M.43 °C热针刺激对帕金森病大鼠的下行促进作用无明显影响，但可显著增加阿朴吗啡诱导的大鼠的下行抑制，并逆转阿朴吗啡诱导的大鼠旋转次数的增加(P<； )，这种作用可被丘脑Vm核多巴胺受体拮抗剂雷氯普利剂量依赖性地减弱(P<； 0.05)。提示早期帕金森病患者下行促进作用增强，下行抑制作用减弱。从临床角度来看，43 °C热疗方案有望选择性地增强下行抑制，同时改善帕金森病患者的运动功能障碍。
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.