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.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Leslie
T A
TA
Department of Anatomy & Developmental Biology, University College London, U.K.
Emson
P C
PC
Dowd
P M
PM
Woolf
C J
CJ
D000818:Animals; D019922:GAP-43 Protein; D017950:Ganglia, Sensory / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015320:Tachykinins / Q000378:metabolism; D015854:Up-Regulation
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin