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神经肽基因表达与辣椒素敏感的初级传入神经：大鼠佐剂性关节炎的维持与扩散

Neuropeptide gene expression and capsaicin-sensitive primary afferents: maintenance and spread of adjuvant arthritis in the rat.

作者信息

Donaldson L F, McQueen D S, Seckl J R

机构信息

Department of Medicine, Western General Hospital, Edinburgh, UK.

出版信息

J Physiol. 1995 Jul 15;486 ( Pt 2)(Pt 2):473-82. doi: 10.1113/jphysiol.1995.sp020826.

DOI:10.1113/jphysiol.1995.sp020826
PMID:7473211
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1156535/
Abstract
  1. Many experimental and clinical arthritides are characterized by their bilateral nature. There is strong evidence to suggest that this bilateral spread may be mediated by a neuronal mechanism. We have previously shown early and sustained induction of mRNAs encoding preprotachykinin (PPT) and calcitonin gene-related peptide (CGRP) in dorsal root ganglion (DRG) neurons innervating an inflamed, arthritic joint. We have now investigated the involvement of capsaicin-sensitive primary afferents and the expression of neuropeptide mRNAs in the maintenance and bilateral spread of mild adjuvant-induced arthritis in the rat. 2. Capsaicin was applied perineurally to either the left (Cap-L) or right (Cap-R) sciatic nerve of halothane-anaesthetized male Han Wistar rats. Two weeks after capsaicin lesioning, arthritis was induced by injection of Freund's complete adjuvant (FCA) around the left ankle at a dose that caused inflammation of the left ankle joint, and a delayed (14 days) contralateral (right) ankle arthritis. Arthritis was monitored for 15 days after injection, when animals were killed and the lumbar DRG dissected. PPT, CGRP, somatostatin (SS), and vasoactive intestinal polypeptide (VIP) mRNA expression was determined in L5 DRG using in situ hybridization. 3. Spread of inflammation/arthritis to the right limb was associated with bilateral rises in PPT and CGRP mRNA expression in L5 DRG. SS mRNA expression in right DRG was unaffected by spread of inflammation. FCA-L+Cap-L reduced left joint swelling and prevented spread of arthritis to the right joint when assessed by joint swelling. This inhibition of spread of arthritis was associated with significant reductions in all left L5 DRG neuropeptide mRNAs compared with controls, and the rise in right L5 DRG PPT mRNA expression seen in FCA-L-alone animals was blocked. FCA-L+Cap-R also reduced left joint swelling and prevented the spread of inflammation to the right ankle. This lesion prevented the rise in PPT and CGRP mRNA expression seen in right DRG with FCA-L alone. 4. These findings suggest a role for capsaicin-sensitive primary afferents and the primary afferent neuropeptides encoded by PPT and CGRP mRNA in the maintenance and spread of arthritis.
摘要
  1. 许多实验性和临床性关节炎都具有双侧性的特点。有充分证据表明，这种双侧扩散可能是由一种神经元机制介导的。我们之前已经证明，在支配发炎的关节炎关节的背根神经节（DRG）神经元中，编码前速激肽原（PPT）和降钙素基因相关肽（CGRP）的mRNA会被早期且持续地诱导。我们现在研究了辣椒素敏感的初级传入神经的参与情况以及神经肽mRNA的表达在大鼠轻度佐剂诱导性关节炎的维持和双侧扩散中的作用。2. 对氟烷麻醉的雄性汉·威斯塔大鼠的左侧（Cap-L）或右侧（Cap-R）坐骨神经进行神经周围注射辣椒素。辣椒素损伤两周后，通过在左踝关节周围注射弗氏完全佐剂（FCA）诱导关节炎，注射剂量会导致左踝关节发炎，并引发延迟（14天）的对侧（右）踝关节关节炎。注射后监测关节炎15天，之后处死动物并解剖腰段DRG。使用原位杂交法测定L5 DRG中PPT、CGRP、生长抑素（SS）和血管活性肠肽（VIP）mRNA的表达。3. 炎症/关节炎向右侧肢体的扩散与L5 DRG中PPT和CGRP mRNA表达的双侧升高有关。右侧DRG中SS mRNA的表达不受炎症扩散的影响。当通过关节肿胀评估时，FCA-L + Cap-L减轻了左关节肿胀，并防止了关节炎向右侧关节的扩散。与对照组相比，这种对关节炎扩散的抑制与所有左侧L5 DRG神经肽mRNA的显著降低有关，并且在仅接受FCA-L处理的动物中观察到的右侧L5 DRG中PPT mRNA表达的升高被阻断。FCA-L + Cap-R也减轻了左关节肿胀，并防止了炎症向右侧踝关节的扩散。这种损伤阻止了仅接受FCA-L处理时在右侧DRG中观察到的PPT和CGRP mRNA表达的升高。4. 这些发现表明，辣椒素敏感的初级传入神经以及由PPT和CGRP mRNA编码的初级传入神经肽在关节炎的维持和扩散中发挥作用。
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b41/1156535/3714d21747ba/jphysiol00316-0208-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b41/1156535/3714d21747ba/jphysiol00316-0208-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b41/1156535/3714d21747ba/jphysiol00316-0208-a.jpg

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