Department of Dental Anesthesiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
PLoS One. 2024 Aug 20;19(8):e0300081. doi: 10.1371/journal.pone.0300081. eCollection 2024.
Pain is a major non-motor symptom of Parkinson's disease (PD). Alterations in the descending pain inhibitory system (DPIS) have been reported to trigger hyperalgesia in PD patients. However, the underlying mechanisms remain unclear. In the current study, dopaminergic nigrostriatal lesions were induced in rats by injecting 6-hydroxydopamine (6-OHDA) into their medial forebrain bundle. The neural mechanisms underlying changes in nociception in the orofacial region of 6-OHDA-lesioned rats was examined by injecting formalin into the vibrissa pad. The 6-OHDA-lesioned rats were seen to exhibit increased frequency of face-rubbing and more c-Fos immunoreactive (c-Fos-IR) cells in the trigeminal spinal subnucleus caudalis (Vc), confirming hyperalgesia. Examination of the number of c-Fos-IR cells in the DPIS nuclei [including the midbrain ventrolateral periaqueductal gray, the locus coeruleus, the nucleus raphe magnus, and paraventricular nucleus (PVN)] showed that 6-OHDA-lesioned rats exhibited a significantly lower number of c-Fos-IR cells in the magnocellular division of the PVN (mPVN) after formalin injection compared to sham-operated rats. Moreover, the 6-OHDA-lesioned rats also exhibited significantly lower plasma oxytocin (OT) concentration and percentage of oxytocin-immunoreactive (OT-IR) neurons expressing c-Fos protein in the mPVN and dorsal parvocellular division of the PVN (dpPVN), which secrete the analgesic hormone OT upon activation by nociceptive stimuli, when compared to the sham-operated rats. The effect of OT on hyperalgesia in 6-OHDA-lesioned rats was examined by injecting formalin into the vibrissa pad after intracisternal administration of OT, and the findings showed a decrease in the frequency of face rubbing and the number of c-Fos-IR cells in the Vc. In conclusion, these findings confirm presence of hyperalgesia in PD rats, potentially due to suppression of the analgesic effects of OT originating from the PVN.
疼痛是帕金森病（PD）的主要非运动症状。据报道，下行疼痛抑制系统（DPIS）的改变会引发 PD 患者的痛觉过敏。然而，其潜在机制尚不清楚。在本研究中，通过将 6-羟多巴胺（6-OHDA）注入内侧前脑束，在大鼠中诱导多巴胺能黑质纹状体病变。通过向触须垫注射福尔马林，研究了 6-OHDA 损伤大鼠口腔区域痛觉变化的神经机制。结果发现，6-OHDA 损伤大鼠出现面部摩擦频率增加，三叉神经脊亚核尾端（Vc）中 c-Fos 免疫反应（c-Fos-IR）细胞增多，证实存在痛觉过敏。检查 DPIS 核[包括中脑腹外侧导水管周围灰质、蓝斑、巨细胞脑桥核和室旁核（PVN）]中 c-Fos-IR 细胞的数量发现，与假手术大鼠相比，福尔马林注射后 6-OHDA 损伤大鼠的 PVN 大细胞部（mPVN）中 c-Fos-IR 细胞数量明显减少。此外，与假手术大鼠相比，6-OHDA 损伤大鼠的 mPVN 和背侧小细胞部（dpPVN）中血浆催产素（OT）浓度和表达 c-Fos 蛋白的催产素免疫反应（OT-IR）神经元的百分比也明显降低，当这些神经元受到伤害性刺激激活时，会分泌镇痛激素 OT。通过向脑室内给予 OT 后向触须垫注射福尔马林，研究了 OT 对 6-OHDA 损伤大鼠痛觉过敏的影响，结果显示 Vc 中的面部摩擦频率和 c-Fos-IR 细胞数量减少。总之，这些发现证实了 PD 大鼠存在痛觉过敏，可能是由于 PVN 来源的 OT 的镇痛作用受到抑制。
