Mason P, Back S A, Fields H L
Department of Neurology, University of California, San Francisco 94143.
J Neurosci. 1992 Oct;12(10):4023-36. doi: 10.1523/JNEUROSCI.12-10-04023.1992.
Neurons in the rostral ventromedial medulla (RVM) are important in the opioid modulation of dorsal horn nociceptive transmission. Systemically administered morphine inhibits one class of RVM cells, the on-cells; excites a second class of RVM cells, the off-cells; and has no effect on a third class, neutral cells. In contrast, iontophoretic application of morphine inhibits on-cells but does not alter the activity of either off- or neutral cells. The present study addresses whether the differential sensitivity to exogenous opioids is correlated with a differential termination pattern onto the three classes of RVM neurons by afferents containing endogenous opioids. Intracellular recordings were made from RVM neurons in rats under light halothane anesthesia. Physiologically characterized neurons were injected with Neurobiotin and then subsequently visualized with a Texas red fluorophore. Thick (50 microns) sections containing labeled RVM cells were processed for enkephalin immunoreactivity (ENK-IR) using an FITC fluorophore and then optically sectioned at 1.5 micron intervals using a dual-channel confocal laser scanning microscope. ENK-IR appositions were found on the somata and dendrites of all on-cells. Although ENK-IR varicosities were also apparently apposed to off- and neutral cells, the density of such appositions was significantly less than the density of ENK-IR appositions onto on-cells. The greater overall density of ENK-IR appositions onto on-cells was apparently due to a concentration of appositions on the soma and proximal dendrites of these neurons. These results support a model of RVM function in which endogenous opioid peptides produce an antinociceptive action by a direct inhibitory action on on-cells that facilitate nociceptive transmission. This on-cell inhibition may produce an additional antinociceptive effect by removing a possible on-cell inhibition of off-cells, which are thought to inhibit nociceptive transmission.
延髓头端腹内侧区（RVM）的神经元在阿片类物质对背角伤害性信息传递的调节中起重要作用。全身给药吗啡可抑制一类RVM细胞，即开细胞；兴奋另一类RVM细胞，即关细胞；对第三类细胞，即中性细胞则无影响。相比之下，离子导入吗啡可抑制开细胞，但不改变关细胞或中性细胞的活性。本研究探讨对外源性阿片类物质的不同敏感性是否与含内源性阿片类物质的传入纤维对三类RVM神经元的不同终末模式相关。在轻度氟烷麻醉下对大鼠的RVM神经元进行细胞内记录。对生理特性明确的神经元注射神经生物素，随后用德克萨斯红荧光团进行可视化。使用FITC荧光团对含有标记RVM细胞的厚（50微米）切片进行脑啡肽免疫反应性（ENK-IR）处理，然后使用双通道共聚焦激光扫描显微镜以1.5微米间隔进行光学切片。在所有开细胞的胞体和树突上均发现有ENK-IR同位。虽然ENK-IR曲张体也明显与关细胞和中性细胞同位，但此类同位的密度明显低于开细胞上ENK-IR同位的密度。开细胞上ENK-IR同位的总体密度更高显然是由于这些神经元的胞体和近端树突上同位的集中分布。这些结果支持一种RVM功能模型，即内源性阿片肽通过对促进伤害性信息传递的开细胞的直接抑制作用产生抗伤害感受作用。这种开细胞抑制可能通过消除对被认为抑制伤害性信息传递的关细胞的可能的开细胞抑制而产生额外的抗伤害感受作用。
