NEUROPEPTIDE GENE-EXPRESSION AND CAPSAICIN-SENSITIVE PRIMARY AFFERENTS - MAINTENANCE AND SPREAD OF ADJUVANT ARTHRITIS IN THE RAT
NEUROPEPTIDE GENE-EXPRESSION AND CAPSAICIN-SENSITIVE PRIMARY AFFERENTS - MAINTENANCE AND SPREAD OF ADJUVANT ARTHRITIS IN THE RAT
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DOI：
10.1113/jphysiol.1995.sp020826
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发表时间：
1995-07-15
影响因子：
5.5
通讯作者：
SECKL, JR
中科院分区：
文献类型：
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作者：
DONALDSON, LF;MCQUEEN, DS;SECKL, JR
1. 许多实验。临床关节炎的特点是双侧发病。有强有力的证据表明，这种双侧扩散可能是由神经元机制介导的。我们之前已经发现，在支配炎症关节炎关节的背根神经节（DRG）神经元中，编码前原激肽（PPT）和降钙素基因相关肽（CGRP）的mrna可以被早期和持续诱导。我们现在已经研究了辣椒素敏感的初级事件和神经肽mrna的表达在大鼠轻度佐剂诱导的关节炎的维持和双侧扩散中的作用。在氟烷麻醉的雄性汉族Wistar大鼠的左（Cap-L）或右（Cap-R）坐骨神经周围施加辣椒素。辣椒素损伤两周后，在左踝关节周围注射弗氏完全佐剂（BCA）诱导关节炎，剂量引起左踝关节炎症，并延迟（14天）对侧（右）踝关节关节炎。注射后监测关节炎15天，处死动物，解剖腰椎DRG。2 .采用原位杂交法检测L5 DRG中PPT、CGRP、生长抑素（SS）和血管活性肠多肽（VIP） mRNA的表达。炎症/关节炎向右肢的扩散与双侧L5 DRG中PPT和CGRP mRNA表达升高有关。右侧DRG中SS mRNA的表达不受炎症扩散的影响。通过关节肿胀评估，FCA-L + Cap-L可减少左关节肿胀，防止关节炎向右关节扩散。与对照组相比，这种对关节炎传播的抑制与所有左侧L5 DRG神经肽mRNA的显著降低有关，并且在单独使用fca - l的动物中，右侧L5 DRG PPT mRNA表达的升高被阻断。FCA-L + Cap-R还能减轻左关节肿胀，防止炎症向右脚踝扩散。FCA-L可抑制右侧DRG中PPT和CGRP mRNA表达的升高。这些发现提示辣椒素敏感的初级传入神经和由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起作用。
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 (BCA) 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.