NERVE GROWTH-FACTOR CONTRIBUTES TO THE UP-REGULATION OF GROWTH-ASSOCIATED PROTEIN-43 AND PREPROTACHYKININ-A MESSENGER-RNAS IN PRIMARY SENSORY NEURONS FOLLOWING PERIPHERAL INFLAMMATION
NERVE GROWTH-FACTOR CONTRIBUTES TO THE UP-REGULATION OF GROWTH-ASSOCIATED PROTEIN-43 AND PREPROTACHYKININ-A MESSENGER-RNAS IN PRIMARY SENSORY NEURONS FOLLOWING PERIPHERAL INFLAMMATION
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DOI：
10.1016/0306-4522(95)00101-n
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发表时间：
1995-08-01
期刊：
影响因子：
3.3
通讯作者：
WOOLF, CJ
中科院分区：
文献类型：
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作者：
LESLIE, TA;EMSON, PC;WOOLF, CJ
在成年大鼠足底注射完全弗氏佐剂诱导的外周炎症导致神经生长相关蛋白43和P物质前体前原激肽a的信使rna在支配炎症区域的背根神经节感觉神经元中的表达迅速（6小时）增加。这种增加在48小时达到顶峰，然后在5天内下降。这种变化存在于支配炎症皮肤的背根神经节细胞（腰4或腰5），但在支配邻近非炎症皮肤的第三腰椎背根神经节中未发现升高。背根神经节中生长相关蛋白43信使RNA的增加伴随着炎症皮肤表皮中生长相关蛋白43样免疫反应纤维的显著增加。在炎症发生前立即全身性给予中和性抗神经生长因子抗体，可防止感觉神经元中生长相关蛋白43和前原激肽A信使rna的增加。在后爪皮下注射神经生长因子（200 ng）可在注射后48小时提高前肢促肽A，但不能提高第四腰椎背根神经节中的生长相关蛋白43信使RNA，这可以通过联合给药抗神经生长因子血清来预防。炎症靶组织中神经生长因子的产生导致反应性成人初级感觉神经元表型的改变，包括生长相关蛋白和肽神经调节剂水平的变化。这提出了炎症及其相关的超敏反应可能涉及感觉神经元生长状态和神经肽含量的改变的可能性。
Peripheral inflammation induced in adult rats by an intraplantar injection of complete Freund's adjuvant results in a rapid (6 h) increase in the expression of the messenger RNAs for the neuronal growth-associated protein 43 and for preprotachykinin A, the precursor for substance P, in dorsal root ganglion sensory neurons innervating the inflamed area. This increase peaks at 48 h and then declines by five days. The changes are present in the dorsal root ganglion cells innervating the inflamed skin (lumbar 4 or 5) but no elevation was found in the third lumbar dorsal root ganglion which innervates neighbouring non-inflamed skin. The increased growth-associated protein 43 messenger RNA in the dorsal root ganglion is followed by a marked increase in growth-associated protein 43-like immunoreactive fibres in the epidermis of the inflamed skin. Systemic administration of neutralizing anti-nerve growth factor antibodies immediately prior to the inflammation prevents the increase in growth-associated protein 43 and preprotachykinin A messenger RNAs in the sensory neurons. A subcutaneous injection of nerve growth factor (200 ng) into the hindpaw elevates preprotachykinin A but not growth-associated protein 43 messenger RNA in the fourth lumbar dorsal root ganglion 48 h post-injection and this could be prevented by co-administration of the anti-nerve growth factor serum. The production of nerve growth factor in inflamed target tissues leads to alterations in the phenotype of responsive adult primary sensory neurons which include a change in the levels of a growth-related protein and a peptide neuromodulator.This raises the possibility that inflammation and its associated hypersensitivity may involve both an alteration in the growth status of sensory neurons and in their neuropeptide content.