Center for Translational Medicine Research on Sensory-Motor Diseases, Yan'an University, Yan'an 716000, PR China; Key Laboratory of Yan'an Sports Rehabilitation Medicine, Yan'an 716000, PR China.
Department of Rehabilitation Medicine, Affiliated Hospital of Yan'an University, Yan'an 716000, PR China.
Exp Neurol. 2024 Sep;379:114846. doi: 10.1016/j.expneurol.2024.114846. Epub 2024 Jun 13.
Pain in Parkinson's disease (PD) has been validated as one of the major non-motor dysfunctions affecting the quality of life and subsequent rehabilitation. In the present study, we investigated the role of the dopamine D3 receptor in the thalamic mediodorsal (MD) and ventromedial (VM) nuclei mediated descending control of nociception and intramuscular (i.m.) 2.5% formalin-induced persistent muscle nociception. Paw withdrawal reflexes were measured in naive rats and rats subjected to PD induced by unilateral microinjection of 6 μg 6-OHDA into the rat striatum. Formalin-induced muscle nociception in phase 1, inter-phase, and phase 2 was significantly greater in PD rats compared to naive and vehicle-treated rats (P < 0.001). PD rats exhibited bilaterally mechanical hyperalgesia and heat hypoalgesia in formalin-induced muscle nociception. Microinjection of SK609, a dopamine D3 receptor agonist, at various doses (2.5-7.5 nmol/0.5 μl) into the thalamic VM nucleus dose-dependently prolonged heat-evoked paw withdrawal latencies in both naive and PD rats. Administration of SK609 to either the MD or VM nuclei had no effect on noxious mechanically evoked paw withdrawal reflexes. Pre-treatment of the thalamic MD nucleus with SK609 significantly attenuated formalin-induced nociception, and reversed mechanical hyperalgesia, but not heat hypoalgesia. Pre-treatment of the thalamic VM nucleus with SK609 inhibited formalin-induced nociception in the late phase of phase 2 (30-75 min) and heat hypoalgesia, but not mechanical hyperalgesia (P < 0.05). It is suggested that the dopamine D3 receptors in the thalamus play an antinociceptive role in the descending modulation of nociception. Activation of D3 receptors within the thalamic MD and VM nuclei attenuates descending facilitation and enhances descending inhibition in rats during PD.
帕金森病（PD）的疼痛已被证实是影响生活质量和后续康复的主要非运动功能障碍之一。在本研究中，我们研究了多巴胺 D3 受体在丘脑内侧背核（MD）和腹内侧核（VM）介导的伤害性感受下行控制中的作用，以及 2.5%福尔马林诱导的持续性肌肉伤害性感受。在未处理的大鼠和单侧向大鼠纹状体注射 6μg 6-OHDA 诱导 PD 的大鼠中测量了爪回缩反射。与未处理的大鼠和载体处理的大鼠相比，PD 大鼠的福尔马林诱导的肌肉伤害感受在 1 相、相间和 2 相明显更大（P < 0.001）。PD 大鼠在福尔马林诱导的肌肉伤害感受中表现出双侧机械性痛觉过敏和热痛觉减退。将多巴胺 D3 受体激动剂 SK609 以不同剂量（2.5-7.5 nmol/0.5 μl）注射到丘脑 VM 核，可剂量依赖性地延长未处理的和 PD 大鼠的热诱发爪回缩潜伏期。将 SK609 给药于 MD 或 VM 核均对有害机械诱发的爪回缩反射没有影响。在丘脑 MD 核预处理 SK609 可显著减轻福尔马林诱导的伤害感受，并逆转机械性痛觉过敏，但不能逆转热痛觉减退。在丘脑 VM 核预处理 SK609 可抑制福尔马林诱导的伤害感受在 2 相的后期（30-75 分钟）和热痛觉减退，但不能抑制机械性痛觉过敏（P < 0.05）。这表明丘脑内的多巴胺 D3 受体在伤害性感受的下行调制中发挥镇痛作用。在 PD 期间，激活丘脑 MD 和 VM 核内的 D3 受体可减弱下行促进作用并增强下行抑制作用。
