Long-lasting regulation of galanin, opioid, and other peptides in dorsal root ganglia and spinal cord during experimental polyarthritis

Long-lasting regulation of galanin, opioid, and other peptides in dorsal root ganglia and spinal cord during experimental polyarthritis
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DOI:
10.1006/exnr.2000.7442
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发表时间:
2000-08-01
影响因子:
5.3
通讯作者:
Hökfelt, T
Hökfelt, T
中科院分区:
医学2区
文献类型:
--
作者:
Calzà, L;Pozza, M;Hökfelt, T

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从急性疼痛过渡到慢性疼痛的机制仍然没有得到很好的理解,我们在治疗上影响这种过渡的手段是有限的。此外,关于长时间暴露于疼痛刺激对表型变化和疼痛体验的长期影响,我们所知甚少。在这项研究中,我们分析了皮内尾注射热杀丁酸分枝杆菌悬浮在完全弗氏佐剂中的长期行为和神经化学效应。研究急性期(21-)和缓解期(注射后79 d)多关节炎大鼠背根神经节降钙素基因相关肽(CGRP)和甘丙氨酸mRNA水平,脊髓内阿片肽mRNA和受体的变化。在关节炎急性期观察到的大多数肽mRNA水平的增加在缓解期仍然存在。因此,当动物不表现自发性疼痛行为和炎症时,DRGs中的CGRP和丙氨酸mrna以及脊髓中的阿片肽mrna和阿片受体仍然被强烈上调。在缓解期进行纳洛酮存在下的热板试验,表明阿片类药物参与长时间疼痛状态后的痛阈调节。最后,x线检查显示关节结构完全破坏,提示平行周围神经末梢病变。这些结果表明,在慢性关节炎症的缓解阶段,几种类型的机制被激活,旨在对抗炎症性和神经性疼痛。因此,背角中的阿片系统以及DRG中的丙氨酸;神经元被上调,两者交替疼痛。(C) 2000年学术出版社。
Mechanisms involved in transition from acute to chronic pain are still not well understood and our means to therapeutically influence this transition are limited. Moreover, very little is known about longlasting consequences of prolonged exposure to painful stimuli with regard to phenotypic changes and pain experience. In this study we have analyzed long term behavioral and neurochemical effects of intradermal tail injection of heat-killed mycobacterium butyricum suspended in complete Freund's adjuvant. Calcitonin gene-related peptide (CGRP) and galanin mRNA levels were investigated in dorsal root ganglia of polyarthritic rats during the acute (21-) and the remission stage (79 days postinjection), and opioid peptide mRNAs and receptors were studied in the spinal cord. Most of the increases in peptide mRNA levels observed during the acute stage of arthritis were still present in the remission stages. Thus, CGRP and galanin mRNAs in DRGs, and opioid peptide mRNAs and opioid receptors in the spinal cord were still strongly up-regulated, when animals do not exhibit spontaneous pain behavior and inflammation. Hot-plate test in the presence of naloxone, performed in the remission stage, indicated that opiates participate in pain threshold regulation after prolonged painful condition. Finally, X-ray examination revealed a complete destruction of joint structure, thus suggesting a parallel lesion of peripheral nerve endings. These results suggest that in the remission stage of chronic joint inflammation several types of mechanisms are activated aiming at counteracting both inflammatory and neuropathic pain. Thus, opioid systems in the dorsal horn as well as galanin in DRG; neurons are upregulated, both alternating pain. (C) 2000 Academic Press.