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Hypothalamic Paraventricular Stimulation Inhibits Nociceptive Wide Dynamic Range Trigeminocervical Complex Cells via Oxytocinergic Transmission
Journal of Neuroscience ( IF 5.3 ) Pub Date : 2024-04-24 , DOI: 10.1523/jneurosci.1501-23.2024
Miguel Condés-Lara , Guadalupe Martínez-Lorenzana , Antonio Espinosa de los Monteros-Zúñiga , Gustavo López-Córdoba , Aketzalli Córdova-Quiroga , Shakty A. Flores-Bojorquez , Abimael González-Hernández

Oxytocinergic transmission blocks nociception at the peripheral, spinal, and supraspinal levels through the oxytocin receptor (OTR). Indeed, a neuronal pathway from the hypothalamic paraventricular nucleus (PVN) to the spinal cord and trigeminal nucleus caudalis (Sp5c) has been described. Hence, although the trigeminocervical complex (TCC), an anatomical area spanning the Sp5c, C1, and C2 regions, plays a role in some pain disorders associated with craniofacial structures (e.g., migraine), the role of oxytocinergic transmission in modulating nociception at this level has been poorly explored. Hence, in vivo electrophysiological recordings of TCC wide dynamic range (WDR) cells sensitive to stimulation of the periorbital or meningeal region were performed in male Wistar rats. PVN electrical stimulation diminished the neuronal firing evoked by periorbital or meningeal electrical stimulation; this inhibition was reversed by OTR antagonists administered locally. Accordingly, neuronal projections (using Fluoro-Ruby) from the PVN to the WDR cells filled with Neurobiotin were observed. Moreover, colocalization between OTR and calcitonin gene–related peptide (CGRP) or OTR and GABA was found near Neurobiotin-filled WDR cells. Retrograde neuronal tracers deposited at the meningeal (True-Blue, TB) and infraorbital nerves (Fluoro-Gold, FG) showed that at the trigeminal ganglion (TG), some cells were immunopositive to both fluorophores, suggesting that some TG cells send projections via the V1 and V2 trigeminal branches. Together, these data may imply that endogenous oxytocinergic transmission inhibits the nociceptive activity of second-order neurons via OTR activation in CGRPergic (primary afferent fibers) and GABAergic cells.



中文翻译:

下丘脑室旁刺激通过催产素能传递抑制伤害性宽动态范围三叉颈复合体细胞

催产素能传递通过催产素受体(OTR)阻断外周、脊髓和脊髓上水平的伤害感受。事实上,从下丘脑室旁核(PVN)到脊髓和三叉神经尾核(Sp5c)的神经元通路已经被描述。因此,尽管三叉颈复合体(TCC)(跨越 Sp5c、C1 和 C2 区域的解剖区域)在一些与颅面结构相关的疼痛疾病(例如偏头痛)中发挥作用,但催产素能传递在调节伤害感受中的作用水平尚未得到很好的探索。因此,在雄性 Wistar 大鼠中进行了对眼眶周围或脑膜区域刺激敏感的 TCC 宽动态范围 (WDR) 细胞的体内电生理记录。 PVN 电刺激减弱了眶周或脑膜电刺激引起的神经元放电;这种抑制作用可以被局部施用的 OTR 拮抗剂逆转。因此,观察到从 PVN 到充满神经生物素的 WDR 细胞的神经元投射(使用 Fluoro-Ruby)。此外,在神经生物素填充的 WDR 细胞附近发现了 OTR 和降钙素基因相关肽 (CGRP) 或 OTR 和 GABA 之间的共定位。沉积在脑膜(True-Blue,TB)和眶下神经(Fluoro-Gold,FG)处的逆行神经元示踪剂显示,在三叉神经节(TG),一些细胞对两种荧光团均呈免疫阳性,这表明一些 TG 细胞通过V1 和 V2 三叉神经支。总之,这些数据可能意味着内源性催产素能传递通过 CGRPergic(初级传入纤维)和 GABA 能细胞中的 OTR 激活抑制二级神经元的伤害性活动。

更新日期:2024-04-25
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