Braz João Manuel, Basbaum Allan I
Department of Anatomy, University of California San Francisco, San Francisco, California 94158, USA.
J Comp Neurol. 2008 Apr 20;507(6):1990-2003. doi: 10.1002/cne.21665.
Despite the evidence for a significant contribution of brainstem serotonergic (5HT) systems to the control of spinal cord "pain" transmission neurons, attention has turned recently to the influence of nonserotonergic neurons, including the facilitatory and inhibitory controls that originate from so-called "on" and "off" cells of the rostroventral medulla (RVM). Unclear, however, is the extent to which these latter circuits interact with or are influenced by the serotonergic cell groups. To address this question we selectively targeted expression of a transneuronal tracer, wheat germ agglutinin (WGA), in the 5HT neurons so as to study the interplay between the 5HT and non-5HT systems. In addition to confirming the direct medullary 5HT projection to the spinal cord we also observed large numbers of non-5HT neurons, in the medullary nucleus reticularis gigantocellularis and magnocellularis, that were WGA-immunoreactive, i.e., were transneuronally labeled from 5HT neurons. FluoroGold injections into the spinal cord established that these reticular neurons are not only postsynaptic to the 5HT neurons of the medulla, but that most are also at the origin of descending, bulbospinal pathways. By contrast, we found no evidence that neurons of the midbrain periaqueductal gray that project to the RVM are postsynaptic to midbrain or medullary 5HT neurons. Finally, we found very few examples of WGA-immunoreactive noradrenergic neurons, which suggests that there is considerable independence of the monoaminergic bulbospinal pathways. Our results indicate that 5HT neurons influence "pain" processing at the spinal cord level both directly and indirectly via feedforward connections with multiple non-5HT descending control pathways.
尽管有证据表明脑干5-羟色胺能（5HT）系统在控制脊髓“疼痛”传递神经元方面发挥了重要作用，但最近人们的注意力已转向非5-羟色胺能神经元的影响，包括源自延髓头端腹内侧（RVM）所谓“开”和“关”细胞的易化性和抑制性控制。然而，尚不清楚这些后一种回路与5-羟色胺能细胞群相互作用的程度，或受其影响的程度。为了解决这个问题，我们选择性地将跨神经元示踪剂小麦胚凝集素（WGA）靶向表达于5HT神经元中，以便研究5HT和非5HT系统之间的相互作用。除了证实延髓5HT直接投射到脊髓外，我们还在延髓巨细胞网状核和大细胞网状核中观察到大量非5HT神经元，它们是WGA免疫反应性的，即从5HT神经元进行跨神经元标记。向脊髓注射荧光金证实，这些网状神经元不仅是延髓5HT神经元的突触后神经元，而且大多数也是下行性延髓脊髓通路的起源。相比之下，我们没有发现投射到RVM的中脑导水管周围灰质神经元是中脑或延髓5HT神经元突触后神经元的证据。最后，我们发现WGA免疫反应性去甲肾上腺素能神经元的例子非常少，这表明单胺能延髓脊髓通路有相当大的独立性。我们的结果表明，5HT神经元通过与多种非5HT下行控制通路的前馈连接，直接和间接地影响脊髓水平的“疼痛”处理。
