Iadarola M J, Douglass J, Civelli O, Naranjo J R
Neurobiology and Anesthesiology Branch, National Institute of Dental Research, Bethesda, MD 20892.
Brain Res. 1988 Jul 12;455(2):205-12. doi: 10.1016/0006-8993(88)90078-9.
A unilateral experimental inflammation of the hindlimb produces hyperalgesia to both mechanical and radiant thermal stimuli that is rapid in onset. During this period, parameters of dynorphin biosynthesis are elevated to a much greater degree than those of the enkephalin system. An increase in the content of the peptide dynorphin A(1-8) occurs in the spinal cord segments that receive sensory input from the affected limb. This is accompanied by a rapid (within 24 h) and pronounced increase in the levels of mRNA coding for the dynorphin protein precursor. Maximum elevations (6- to 8-fold) of preprodynorphin mRNA are observed between days 2 and 5 subsequent to the induction of inflammation. Compared to the increase in mRNA, the increase in dynorphin A(1-8) peptide was appreciably delayed and proportionately less; maximal increases in peptide (3-fold) were seen at day 5 of inflammation. Dorsal spinal cord preproenkephalin mRNA is elevated to a lesser degree (50-80%). However, the increase in preproenkephalin mRNA is apparently not enough to yield a measurable increase in the proenkephalin-derived peptide met5-enkephalin-Arg6-Gly7-Leu8, the levels of which showed no significant change during the 14-day inflammatory period. These data suggest the active participation of opioid neurons, especially those containing dynorphin, at the spinal level, in the modulation of sensory afferent input during peripheral inflammatory pain states.
单侧后肢实验性炎症会导致对机械和辐射热刺激均产生痛觉过敏，且起效迅速。在此期间，强啡肽生物合成参数的升高程度远大于脑啡肽系统的参数。在接受来自受影响肢体感觉输入的脊髓节段中，肽强啡肽A(1 - 8)的含量增加。与此同时，编码强啡肽蛋白前体的mRNA水平迅速（在24小时内）且显著升高。在炎症诱导后的第2天至第5天观察到前强啡肽原mRNA的最大升高（6至8倍）。与mRNA的增加相比，强啡肽A(1 - 8)肽的增加明显延迟且程度较小；在炎症第5天观察到肽的最大增加（3倍）。脊髓背侧前脑啡肽原mRNA升高程度较小（50 - 80%）。然而，前脑啡肽原mRNA的增加显然不足以使源自前脑啡肽的肽甲硫氨酸脑啡肽-精氨酸-甘氨酸-亮氨酸的水平产生可测量的增加，其水平在14天的炎症期内未显示出显著变化。这些数据表明阿片样物质神经元，尤其是那些含有强啡肽的神经元，在脊髓水平积极参与外周炎症性疼痛状态下感觉传入输入的调节。
