Parry D M, Macmillan F M, Koutsikou S, McMullan S, Lumb B M
Department of Physiology and Pharmacology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
Neuroscience. 2008 Apr 9;152(4):1076-85. doi: 10.1016/j.neuroscience.2008.01.018. Epub 2008 Jan 19.
This study was designed to determine the organization of nociceptive inputs with different behavioral significance into spinal-brainstem circuits in the rat. Induction of Fos protein was used to localize spinal dorsal horn and hypothalamic neurons activated by noxious heating of the hind paw dorsum at rates known to preferentially activate C- or A-heat nociceptors. This was combined with retrograde transport of cholera toxin subunit B from the dorsolateral/lateral- (DL/L-) or the ventrolateral- (VL-) periaqueductal gray (PAG) in order to map the organization of A- and C-fiber input to spinal-brainstem circuits. The majority of dorsal horn heat-activated neurons were located in laminae I and II. A significantly larger proportion of C-fiber-activated neurons projected to the VL-PAG (P<0.05) compared with its DL/L-sector. In contrast, there was no columnar separation in the projections of A-fiber-activated neurons. However, a significantly greater proportion of A-fiber-activated neurons (P<0.05) were retrogradely labeled from the DL/L-PAG, when compared with C-fiber-activated neurons. A large proportion (25-50%) of A- and C-fiber-activated neurons in the lateral spinal nucleus projected to the PAG. A-fiber-activated neurons were found throughout the rostral hypothalamus but those projecting to the PAG were focused in the lateral area of the anterior hypothalamus (LAAH), from where approximately 20% projected to the VL-PAG, which was significantly more than to the DL/L PAG (P<0.05). We hypothesize that the organization of A- versus C-fiber inputs to the PAG enables the coordination of coping strategies appropriate to meet the demands imposed by these different noxious stimuli. Hypothalamic-PAG projections activated by A-fiber inputs did not reflect this level of organization and we suggest that this may relate to their role in thermoregulation as opposed to autonomic responses to particular nociceptive inputs.
本研究旨在确定大鼠中具有不同行为意义的伤害性传入信号在脊髓-脑干回路中的组织方式。通过诱导Fos蛋白来定位脊髓背角和下丘脑神经元，这些神经元是由已知优先激活C型或A热伤害感受器的后爪背侧有害加热所激活的。这与霍乱毒素B亚基从背外侧/外侧-（DL/L-）或腹外侧-（VL-）导水管周围灰质（PAG）的逆行运输相结合，以绘制A纤维和C纤维输入到脊髓-脑干回路的组织方式。大多数背角热激活神经元位于I层和II层。与DL/L区相比，投射到VL-PAG的C纤维激活神经元比例显著更大（P<0.05）。相反，A纤维激活神经元的投射没有柱状分离。然而，与C纤维激活神经元相比，从DL/L-PAG逆行标记的A纤维激活神经元比例显著更大（P<0.05）。脊髓外侧核中很大一部分（25-50%）A纤维和C纤维激活神经元投射到PAG。在整个下丘脑前部都发现了A纤维激活神经元，但投射到PAG的神经元集中在下丘脑前部外侧区域（LAAH），从该区域约20%投射到VL-PAG，这显著多于投射到DL/L PAG的比例（P<0.05）。我们假设，A纤维与C纤维输入到PAG的组织方式能够协调应对策略，以满足这些不同有害刺激所带来的需求。由A纤维输入激活的下丘脑-PAG投射并未反映出这种组织水平，我们认为这可能与其在体温调节中的作用有关，而不是与对特定伤害性输入的自主反应有关。
