Abstract:
The loss of midbrain dopaminergic (DA) neurons is the fundamental pathological feature of Parkinson\'s disease (PD). PD causes chronic pain in two-thirds of patients. Recent studies showed that the activation of the pedunculopontine tegmental nucleus (PPTg) can effectively relieve inflammatory pain and neuropathic pain. The PPTg is located in the pontomesencephalic tegmentum, a target of deep brain stimulation (DBS) treatment in PD, and is involved in motor control and sensory integration. To test whether the lesion of midbrain DA neurons induced pain hypersensitivity, and whether the chemogenetic activation of the PPTg could modulate the pain, the AAV-hM3Dq receptor was transfected and expressed into the PPTg neurons of 6-hydroxydopamine-lesioned mice. In this study, von Frey, open field, and adhesive tape removal tests were used to assess animals\' pain sensitivity, locomotor activity, and sensorimotor function and somatosensory perception, respectively. Here, we found that the lesion of midbrain DA neurons induced a minor deficit in voluntary movement but did not affect sensorimotor function and somatosensory perception in the tape removal test. The results showed that lesion led to pain hypersensitivity, which could be alleviated both by levodopa and by the chemogenetic activation of the PPTg. Activating the PPTg may be a potential therapeutic strategy to relieve pain phenotypes in PD.
摘要:
中脑多巴胺能(DA)神经元的丢失是帕金森病(PD)的基本病理特征。PD在三分之二的患者中引起慢性疼痛。最近的研究表明,激活桥尖被膜核(PPTg)可以有效缓解炎性疼痛和神经性疼痛。PPTg位于前脑被膜,PD中深部脑刺激(DBS)治疗的目标,并参与运动控制和感觉统合。为了测试中脑DA神经元的损伤是否引起疼痛过敏,以及PPTg的化学激活是否可以调节疼痛,AAV-hM3Dq受体被转染并表达到6-羟基多巴胺损伤小鼠的PPTg神经元中。在这项研究中,冯·弗雷,开放领域,和胶带去除试验用于评估动物的疼痛敏感性,运动活动,感觉运动功能和体感知觉,分别。这里,我们发现,中脑DA神经元的病变在自主运动中引起了轻微的缺陷,但在胶带去除试验中不影响感觉运动功能和体感知觉。结果显示,病变导致疼痛过敏,这可以通过左旋多巴和PPTg的化学遗传活化来缓解。激活PPTg可能是缓解PD疼痛表型的潜在治疗策略。