Tolerance to the antinociceptive properties of morphine in the rat spinal cord: alteration of calcitonin gene-related peptide-like immunostaining and receptor binding sites.
Tolerance to the antinociceptive properties of morphine in the rat spinal cord: alteration of calcitonin gene-related peptide-like immunostaining and receptor binding sites.
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发表时间：
1995-05
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通讯作者：
D. Ménard;D. van Rossum;S. Kar;F. Jolicoeur;K. Jhamandas;R. Quirion
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作者：
D. Ménard;D. van Rossum;S. Kar;F. Jolicoeur;K. Jhamandas;R. Quirion
长期服用吗啡后，对脊髓镇痛作用的耐受性会迅速增强。这种现象的机制尚不清楚，但不太可能是由于脊髓阿片肽及其受体结合位点的直接调节。多种神经肽，特别是神经激肽和降钙素基因相关肽（CGRP）集中在初级感觉传入神经中，因此被认为在脊髓伤害性机制中发挥重要作用。然而，它们在吗啡抗伤害特性耐受性发展中的功能尚未得到充分探索。因此，我们研究了各种感觉神经肽，包括 CGRP、P 物质、甘丙肽、神经降压素和神经肽 Y 及其脊髓背角受体在鞘内吗啡抗伤害作用耐受性发展过程中可能的参与。使用微型渗透泵在腰椎 L4 水平连续施用硫酸吗啡（7.5 微克/微升/小时）3、5、7 和 14 天。通过尾浸试验验证吗啡抗伤害作用的耐受性，并在治疗第 5 天变得明显。在耐受动物中，脊髓背角 I、II 和 III 层中 CGRP 样免疫染色显着增加，[125I]人 CGRP α 结合减少 (30-45%)。这些变化与吗啡耐受的发生同时发生，并持续了 14 天的耐受期。在所研究的其他神经肽的免疫染色或结合中没有观察到类似的变化。（摘要截断为 250 字）
Tolerance to the spinal antinociceptive effects of morphine develops rapidly after its chronic administration. The mechanism involved in this phenomenon is unclear, but it is unlikely due to a direct regulation of spinal opioid peptides and their receptor binding sites. A variety of neuropeptides, especially the neurokinins and calcitonin gene-related peptide (CGRP) are concentrated in primary sensory afferents and have thus been proposed to play significant roles in spinal nociceptive mechanisms. However, their functions in the development of tolerance to the antinociceptive properties of morphine have not been explored fully. We therefore investigated the possible involvement of various sensory neuropeptides including CGRP, substance P, galanin, neurotensin and neuropeptide Y and their receptors in the dorsal horn of the spinal cord during the development of tolerance to the antinociceptive action of intrathecal morphine. Morphine sulfate (7.5 micrograms/microliters/hr) was administered continuously at lumbar level L4 using mini-osmotic pumps for 3, 5, 7 and 14 days. Tolerance to the antinociceptive effect of morphine was verified with the tail-immersion test and became evident on the 5th day of treatment. In tolerant animals, there was a marked increase in CGRP-like immunostaining and a decrease (30-45%) in [125I]human CGRP alpha binding in laminae I, II and III of the dorsal horn of the spinal cord. These changes coincided with the onset of morphine tolerance and persisted for the 14-day period during which tolerance was present. Similar changes were not observed in the immunostaining or binding of the other neuropeptides studied.(ABSTRACT TRUNCATED AT 250 WORDS)