Ikeda Tetsuya, Terayama Ryuji, Jue Seong-Suk, Sugiyo Shinichi, Dubner Ronald, Ren Ke
Department of Oral and Craniofacial Biological Sciences, Dental School, and Program in Neuroscience, University of Maryland, Baltimore, Maryland 21201-1586, USA.
J Comp Neurol. 2003 Oct 13;465(2):220-33. doi: 10.1002/cne.10836.
To understand the functional significance of orofacial injury-induced neuronal activation, this study examined the rostral projection of caudal brainstem neurons that were activated by masseteric inflammation. Rats were injected with a retrograde tracer, Fluorogold, into the nucleus submedius of the thalamus (Sm), parabrachial nucleus (PB), lateral hypothalamus (LH), or medial ventroposterior thalamic nucleus (VPM) 7 days before injection of an inflammatory agent, complete Freund's adjuvant (CFA), into the masseter muscle. Rats were perfused at 2 hours after inflammation, and brainstem tissues were processed for Fos-Fluorogold double immunocytochemistry. Although there was no difference in Fos expression among the four groups (n=4 per site), the rostral projection of Fos-positive neurons showed dramatic differences. In the ventral portion of the trigeminal subnuclei interpolaris/caudalis (Vi/Vc) transition zone, the percentage of Fos-positive neurons projecting to the Sm (39.7%) was significantly higher than that projecting to the LH (5.4%) or VPM (5.6%; P<.001). The anesthesia alone also induced Fos expression in ventral Vi/Vc neurons, but these neurons did not project to Sm. In the caudal laminated Vc and dorsal Vi/Vc, the PB was the major site of rostral projection of Fos-positive neurons. In the caudal ventrolateral medulla and nucleus tractus solitarius, Fos-positive neurons projected to the Sm, PB, and LH. Most VPM-projecting neurons examined did not show Fos-like immunoreactivity after masseter inflammation. These findings emphasize the importance of the trigeminal Vi/Vc transition zone in response to orofacial deep tissue injury. Furthermore, the results differentiate the ventral and dorsal portions of the Vi/Vc transition zone, in that the Sm received projection mainly from activated neurons in the ventral Vi/Vc. The activation of Vi/Vc neurons and associated ascending pathways may facilitate somatoautonomic and somatovisceral integration and descending pain modulation after orofacial deep tissue injury.
为了解口面部损伤诱导的神经元激活的功能意义，本研究检测了因咬肌炎症而被激活的延髓尾端神经元的吻侧投射。在向咬肌注射炎性介质完全弗氏佐剂（CFA）前7天，将逆行示踪剂荧光金注射到大鼠丘脑中介核（Sm）、臂旁核（PB）、下丘脑外侧区（LH）或丘脑腹后内侧核（VPM）。在炎症发生后2小时对大鼠进行灌注，并对脑干组织进行Fos-荧光金双重免疫细胞化学处理。虽然四组之间Fos表达无差异（每个部位n = 4），但Fos阳性神经元的吻侧投射显示出显著差异。在三叉神经中极/尾侧亚核（Vi/Vc）过渡区的腹侧部分，投射到Sm的Fos阳性神经元百分比（39.7%）显著高于投射到LH（5.4%）或VPM（5.6%；P<0.001）的百分比。单独麻醉也可诱导腹侧Vi/Vc神经元表达Fos，但这些神经元不投射到Sm。在尾侧分层的Vc和背侧Vi/Vc中，PB是Fos阳性神经元吻侧投射的主要部位。在尾侧延髓腹外侧和孤束核中，Fos阳性神经元投射到Sm、PB和LH。大多数检测的投射到VPM的神经元在咬肌炎症后未显示Fos样免疫反应性。这些发现强调了三叉神经Vi/Vc过渡区在对口面部深部组织损伤反应中的重要性。此外，结果区分了Vi/Vc过渡区的腹侧和背侧部分，因为Sm主要接收来自腹侧Vi/Vc中激活神经元的投射。Vi/Vc神经元的激活及相关的上行通路可能促进口面部深部组织损伤后的躯体自主和躯体内脏整合以及下行性疼痛调制。
