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

Autor: Piers C. Emson, P.M. Dowd, T A Leslie, Clifford J. Woolf
Rok vydání: 1995
Předmět:
Zdroj: Neuroscience. 67:753-761
ISSN: 0306-4522
DOI: 10.1016/0306-4522(95)00101-n
Popis: Peripheral inflammation induced in adult rats by an intraplantar injection of complete Freund's adjuvant results in a rapid (6h) 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.
Databáze: OpenAIRE