Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson's disease ultimately experienced by the vast majority of patients. This article does not review the increased understanding of dyskinesia pathophysiology we have seen during the past few years but, instead, specifically focuses upon the very first molecular events thought to be responsible for the establishment of dyskinesia and generally grouped under the term of "priming". Priming is classically defined as the process by which the brain becomes sensitized such that administration of a dopaminergic therapy modifies the response to subsequent dopaminergic treatments. In this way, over time, with repeated treatment, the chance of dopaminergic stimulation eliciting dyskinesia is increased and once dyskinesia has been established, the severity of dyskinesia increases. In this opinion review, however, we aim at strongly opposing the common view of priming. We propose, and hopefully will demonstrate, that priming does not exist per se but is the direct and intrinsic consequence of the loss of dopamine innervation of the striatum (and other target structures), meaning that the first injections of dopaminergic drugs only exacerbate those mechanisms (sensitization) but do not induce them. Chronicity and pulsatility of subsequent dopaminergic treatment only exacerbates the likelihood of developing dyskinesia.

中文翻译：

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在帕金森氏病中引发左旋多巴诱发的运动障碍：治疗或疾病固有的功能？

非自愿运动或运动障碍是左旋多巴治疗帕金森氏病最终使绝大多数患者衰弱的并发症。本文并未回顾我们在过去几年中对运动障碍病理生理学的日益了解，而是特别关注了最初被认为与运动障碍建立有关的分子事件，通常将其归为“引发”一词。 。引发被经典地定义为大脑变得敏感的过程，从而使多巴胺能疗法的施用改变了对随后多巴胺能疗法的反应。这样，随着时间的流逝，经过反复的治疗，多巴胺能刺激引起运动障碍的机会增加，一旦建立了运动障碍，运动障碍的严重程度就会增加。但是，在这篇观点综述中，我们的目标是强烈反对启动的普遍观点。我们提议并希望能证明，引发本身并不存在，而是纹状体（和其他靶标结构）多巴胺神经支配力丧失的直接和内在后果，这意味着首次注射多巴胺能药物只会加剧这些机制。 （敏化），但不要诱导它们。随后多巴胺能治疗的慢性和搏动性只会加剧发生运动障碍的可能性。并有望证明，引发本身并不存在，而是纹状体（和其他靶标结构）多巴胺神经支配丧失的直接和内在后果，这意味着多巴胺能药物的首次注射只会加剧这些机制（敏化）但不要诱使他们。随后多巴胺能治疗的慢性和搏动性只会加剧发生运动障碍的可能性。并有望证明，引发本身并不存在，而只是纹状体（和其他靶标结构）多巴胺神经支配能力丧失的直接和内在后果，这意味着多巴胺能药物的首次注射只会加剧这些机制（敏化）但不要诱使他们。随后多巴胺能治疗的慢性和搏动性只会加剧发生运动障碍的可能性。