INCREASED EXPRESSION OF PREPROTACHYKININ, CALCITONIN GENE-RELATED PEPTIDE, BUT NOT VASOACTIVE-INTESTINAL-PEPTIDE MESSENGER-RNA IN DORSAL-ROOT GANGLIA DURING THE DEVELOPMENT OF ADJUVANT MONOARTHRITIS IN THE RAT
INCREASED EXPRESSION OF PREPROTACHYKININ, CALCITONIN GENE-RELATED PEPTIDE, BUT NOT VASOACTIVE-INTESTINAL-PEPTIDE MESSENGER-RNA IN DORSAL-ROOT GANGLIA DURING THE DEVELOPMENT OF ADJUVANT MONOARTHRITIS IN THE RAT
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DOI：
10.1016/0169-328x(92)90204-o
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发表时间：
1992-11-01
期刊：
影响因子：
--
通讯作者：
SECKL, JR
中科院分区：
文献类型：
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作者：
DONALDSON, LF;HARMAR, AJ;SECKL, JR
背根神经节（DRG）中的神经肽参与了实验性和临床关节炎疼痛和神经源性炎症的发病机制。最近，我们证明了在关节炎介导的单关节炎中，P物质（SP）和降钙素基因相关肽（CGRP）的水平升高仅限于支配DRG。我们现在已经研究了肽含量的变化是否反映在神经肽基因表达的改变和所涉及的时间过程中。使用原位杂交，我们发现仅在支配（同侧L5）DRG神经元中β-前速激肽原（PPT; 81 +/- 24%上升）和α-CGRP（44 +/- 6%上升）mRNA的表达显著增加。这些增加发生在急性炎症发作时（8小时），并持续到14天后发展为慢性关节炎。表达PPT或CGRP mRNA的DRG神经元比例无变化。编码血管活性肠多肽（VIP）的信使RNA未被诱导。这些数据表明，在DRG中PPT和CGRP肽的合成增加可能在药物介导的急性炎症和慢性关节炎的发病机制中起作用。
Neuropeptides in dorsal root ganglia (DRG) have been implicated in the pathogenesis of pain and neurogenic inflammation in experimental and clinical arthritis. Recently we demonstrated increased levels of substance P (SP) and calcitonin gene-related peptide (CGRP) confined to innervating DRG in adjuvant-mediated monoarthritis. We have now investigated whether changes in peptide content are reflected in altered neuropeptide gene expression and the time course involved. Using in situ hybridization we found marked increases in expression of beta-preprotachykinin (PPT; 81 +/- 24% rise) and alpha-CGRP (44 +/- 6% rise) mRNAs in innervating (ipsilateral L5) DRG neurones only. These increases occured at the onset of acute inflammation (8 h) and persisted until chronic arthritis developed after 14 days. There were no changes in the proportion of DRG neurones expressing PPT or CGRP mRNAs. Messenger RNA encoding vasoactive intestinal polypeptide (VIP) was not induced. These data suggest that increased synthesis of PPT and CGRP peptides in DRG may play a role in the pathogenesis both of adjuvant-mediated acute inflammation and chronic arthritis.