Dieb Wisam, Ouachikh Omar, Durif Franck, Hafidi Aziz
Laboratoire de neuro-psychopharmacology des systèmes dopaminergiques sous corticaux, Clermont Université, Université d'Auvergne Clermont-Ferrand, EA7280, France.
Laboratoire de neuro-psychopharmacology des systèmes dopaminergiques sous corticaux, Clermont Université, Université d'Auvergne Clermont-Ferrand, EA7280, France ; Service de Neurologie, CHU Clermont-Ferrand Clermont-Ferrand, 63000, France.
Brain Behav. 2014 May;4(3):368-80. doi: 10.1002/brb3.214. Epub 2014 Feb 20.
Pain constitutes the major non motor syndrome in Parkinson's disease (PD) and includes neuropathic pain; however current drug therapies used to alleviate it have only limited efficacy. This is probably due to poor understanding of the mechanisms underlying it.
We investigated a major class of trigeminal neuropathic pain, dynamic mechanical allodynia (DMA), in a rat model of PD and in which a bilateral 6-hydroxy dopamine (6-OHDA) injection was administered to produce a lesion of the nigrostriatal dopaminergic pathway.
Lesioned animals presented significant DMA in the orofacial area that occurred from 4 days to 5 weeks post-injury. To investigate a segmental implication in the neuropathic pain induced by dopamine depletion, the expression of the isoform gamma of the protein kinase C (PKCg) and phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2) was explored in the medullary dorsal horn (MDH). There was a high increase in PKCg expression in the III and IIi laminae of the MDH of lesioned-animals compared to shams. pERK1/2 expression was also significantly high in the ipsilateral MDH of lesioned rats in response to non-noxious tactile stimulus of the orofacial region. Since pERK1/2 is expressed only in response to nociceptive stimuli in the dorsal spinal horn, the current study demonstrates that non-noxious stimuli evoke allodynic response. Intraperitoneal and intracisternal administrations of bromocriptine, a dopamine 2 receptor (D2R) agonist, significantly decreased DMA compared to control rats injected with saline. These data demonstrate for the first time that nigrostriatal dopaminergic depletion produces trigeminal neuropathic pain that at least involves a segmental mechanism. In addition, bromocriptine was shown to have a remarkable analgesic effect on this neuropathic pain symptom.
疼痛是帕金森病（PD）的主要非运动综合征，包括神经性疼痛；然而，目前用于缓解疼痛的药物治疗效果有限。这可能是由于对其潜在机制了解不足。
我们在PD大鼠模型中研究了一类主要的三叉神经神经性疼痛，即动态机械性异常性疼痛（DMA），该模型通过双侧注射6-羟基多巴胺（6-OHDA）造成黑质纹状体多巴胺能通路损伤。
损伤动物在损伤后4天至5周在口面部区域出现明显的DMA。为了研究多巴胺耗竭诱导的神经性疼痛中的节段性影响，我们在延髓背角（MDH）中探究了蛋白激酶C（PKCg）同工型γ和磷酸化细胞外信号调节激酶1/2（pERK1/2）的表达。与假手术组相比，损伤动物MDH的III层和IIi层中PKCg表达显著增加。在口面部区域受到非伤害性触觉刺激时，损伤大鼠同侧MDH中的pERK1/2表达也显著升高。由于pERK1/2仅在脊髓背角对伤害性刺激作出反应时表达，本研究表明非伤害性刺激可诱发异常性疼痛反应。与注射生理盐水的对照大鼠相比，腹腔内和脑池内给予多巴胺2受体（D2R）激动剂溴隐亭可显著降低DMA。这些数据首次证明黑质纹状体多巴胺能耗竭会产生三叉神经神经性疼痛，至少涉及节段性机制。此外，溴隐亭对这种神经性疼痛症状具有显著的镇痛作用。
