Ma W, Ribeiro-da-Silva A, De Koninck Y, Radhakrishnan V, Cuello A C, Henry J L
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Neuroscience. 1997 Apr;77(3):793-811. doi: 10.1016/s0306-4522(96)00510-6.
A combination of intracellular electrophysiological recording and injection of horseradish peroxidase with ultrastructural immunocytochemistry was used to investigate the synaptic interplay between substance P- and enkephalin-immunoreactive axonal boutons and three types of functionally characterized dorsal horn neurons in the cat spinal cord. The dorsal horn neurons were classified as nociceptive specific, wide dynamic range and non-nociceptive based on their responses to innocuous and noxious stimuli. Most of the nociceptive neurons (either nociceptive specific or wide dynamic range) contained enkephalin immunoreactivity, but none of the non-nociceptive neurons were positive for enkephalin. Three types of immunoreactive boutons were found in contact with the functionally characterized dorsal horn neurons. These boutons were positive for either substance P, enkephalin, or substance P+enkephalin. Quantitative analysis revealed that the percentages of substance P-immunoreactive boutons apposed to the cell bodies, proximal dendrites and distal dendrites of nociceptive neurons were significantly higher than those of non-nociceptive neurons. Furthermore, the percentages of substance P+enkephalin-immunoreactive axonal boutons apposed to the distal dendrites of nociceptive neurons were significantly higher than those of non-nociceptive neurons and the percentages of enkephalin-immunoreactive boutons apposed to the cell bodies and proximal dendrites of nociceptive neurons were significantly higher than in non-nociceptive neurons. Finally, neither enkephalin-immunoreactive nor substance P+enkephalin-immunoreactive boutons were ever seen presynaptic to substance P-immunoreactive boutons. These results provide evidence of an anatomical substrate within the dorsal horn for the interaction of substance P-mediated with enkephalin-mediated mechanisms. The data support the idea that the modulation of nociceptive input in the dorsal horn by enkephalinergic neurons occurs mainly via a postsynaptic mechanism, and thus suggest that dorsal horn enkephalinergic neurons participate in a local inhibitory feedback loop in a distinct pathway from the previously postulated opioid-mediated depression of substance P release from primary afferent terminals.
采用细胞内电生理记录、辣根过氧化物酶注射结合超微结构免疫细胞化学的方法，研究了P物质和脑啡肽免疫反应性轴突终扣与猫脊髓中三种功能特性明确的背角神经元之间的突触相互作用。根据背角神经元对无害和有害刺激的反应，将其分为伤害性特异性神经元、广动力范围神经元和非伤害性神经元。大多数伤害性神经元（伤害性特异性神经元或广动力范围神经元）含有脑啡肽免疫反应性，但非伤害性神经元均无脑啡肽阳性。发现有三种类型的免疫反应性终扣与功能特性明确的背角神经元接触。这些终扣对P物质、脑啡肽或P物质+脑啡肽呈阳性。定量分析显示，与伤害性神经元的胞体、近端树突和远端树突相邻的P物质免疫反应性终扣的百分比显著高于非伤害性神经元。此外，与伤害性神经元远端树突相邻的P物质+脑啡肽免疫反应性轴突终扣的百分比显著高于非伤害性神经元，与伤害性神经元胞体和近端树突相邻的脑啡肽免疫反应性终扣的百分比显著高于非伤害性神经元。最后，从未观察到脑啡肽免疫反应性或P物质+脑啡肽免疫反应性终扣位于P物质免疫反应性终扣的突触前。这些结果为背角内P物质介导机制与脑啡肽介导机制相互作用提供了解剖学基础。数据支持这样的观点，即脑啡肽能神经元对背角伤害性传入的调制主要通过突触后机制发生，因此表明背角脑啡肽能神经元参与了一个局部抑制性反馈回路，该回路与先前推测的阿片类药物介导的初级传入终末P物质释放抑制的途径不同。
