Woolf C J
Department of Anatomy and Developmental Biology, University College London, UK.
Philos Trans R Soc Lond B Biol Sci. 1996 Mar 29;351(1338):441-8. doi: 10.1098/rstb.1996.0040.
Inflammation results in an early and maintained elevation in nerve growth factor (NGF) levels in inflamed tissues. Neutralizing the action of the increased NGF with specific anti-NGF antibodies substantially diminishes inflammatory hypersensitivity, indicating that this neurotrophin is a key mediator in the production of inflammatory pain. The hyperalgesic actions of NGF may in part be the consequence of an increase in sensitivity of the peripheral terminals of high threshold nociceptors either as a result of a direct action of NGF on trkA expressing sensory fibres or indirectly via the release of sensitizing mediators from trkA expressing inflammatory cells and postganglionic sympathetic neurons. NGF is also, however, retrogradely transported in sensory neurons to the dorsal root ganglion where it alters transcription of a number of proteins and peptides. This chapter reviews evidence suggesting that an NGF-mediated modification of gene expression in the dorsal root ganglion during inflammation is central to the pathophysiology of persistent pain. The phenotype changes produced by NGF during inflammation include elevation of neuropeptides which may amplify sensory input signals in the spinal cord and augment neurogenic inflammation in the periphery and the upregulation of growth related molecules which may lead to a hyperinnervation of injured tissue by promoting terminal sprouting.
炎症会导致炎症组织中神经生长因子（NGF）水平早期升高并持续维持。用特异性抗NGF抗体中和增加的NGF的作用，可显著减轻炎症性超敏反应，这表明这种神经营养因子是炎症性疼痛产生的关键介质。NGF的痛觉过敏作用部分可能是由于高阈值伤害感受器外周终末敏感性增加所致，这可能是由于NGF对表达trkA的感觉纤维直接作用的结果，或者是通过表达trkA的炎症细胞和节后交感神经元释放敏化介质间接导致的。然而，NGF也会在感觉神经元中逆行运输到背根神经节，在那里它会改变许多蛋白质和肽的转录。本章综述了相关证据，表明炎症期间背根神经节中NGF介导的基因表达修饰是持续性疼痛病理生理学的核心。炎症期间NGF产生的表型变化包括神经肽升高，这可能会放大脊髓中的感觉输入信号并增强外周的神经源性炎症，以及生长相关分子的上调，这可能通过促进终末芽生导致受损组织的神经支配过度。
