OPIOID PEPTIDE GENE EXPRESSION IN NUCLEUS CAUDALIS

表达阿片肽的尾核神经元 神经递质基因前脑啡肽原和前强啡肽原是 显著地牵涉到牙齿和其他 脑干下行初级传入口面痛 系统，甚至是阿片类药物。 然而，这些细节 相互作用和不同的作用，肽来源于 这些基因中的每一个可能在这些过程中发挥作用仍然不清楚。 这项建议将利用最近开发的原位杂交技术 技术，以定量评估的相对水平， 这两个基因在尾核神经元中的表达。 它将 证实了神经元细胞中特定的变化模式， 我们发现这些基因的表达 或刺激三叉神经的初步研究。 这些结果提供了有趣的证据， 前脑啡肽原和前强啡肽原在特异性 神经元亚群对去除原发灶的反应 传入神经，以及对刺激的不同细胞反应 不同直径的纤维。 刺激的影响 下行的疼痛抑制通路起源于 还将评估导水管周围灰质。 最后，影响 阿片激动剂和拮抗剂药物，已发现在 我们的实验室调节这些基因在纹状体的表达， 将在尾核的神经元中评估神经元。 神经元mRNA水平的这些变化可能表明 从表达每种基因的神经元中释放肽 如果翻译、加工、细胞内转运的速率 降解和肽库的大小是稳定的， 设置. 这一信息将增强人们对 这些刺激因素对大脑的影响是复杂的， 尾核神经元的功能提供了至关重要的 牙齿和口面部疼痛的第一级调节。

Nucleus caudalis neurons that express the opioid peptide neurotransmitter genes preproenkephalin and preprodynorphin are prominently implicated in the modulation of dental and other orofacial pain by primary afferent inputs, descending brainstem systems, and even by opiate drugs. However, the details of these interactions and the differential roles that peptides derived from each of these genes might play in these processes remain obscure. This proposal will utilize recently-developed in situ hybridization techniques to quantitatively assess the relative levels of expression of these two genes in nucleus caudalis neurons. It will confirm the specific patterns of alterations in the neuronal expression of each of these genes that we have found after removal or stimulation of the trigeminal nerve in preliminary studies. These results provide intriguing evidence for opposite changes in expression of preproenkephalin and preprodynorphin in specific neuronal subpopulations in response to removal of primary afferents, and of differential cellular responses to stimulation of fibers of different diameters. Influences of stimulation of the descending painsuppressing pathways originating from the periaqueductal grey will also be evaluated. Finally, the impact of the opiate agonist and antagonist drugs that have been found in our laboratories to modulate expression of these genes in striatal neurons will be assessed in neurons of the nucleus caudalis. These changes in neuronal mRNA levels could indicate altered rates of release of peptides from neurons expressing each of the genes if the rates of translation, processing, intracellular transport and degradation and the size of peptide stores were stable in these settings. This information will enhance appreciation of the complex but potentially powerful impact of these stimuli on the function of the nucleus caudalis neurons that provide a crucial first level of modulation of dental and orofacial pain.