Increased expression of GAP-43 in small sensory neurons after stimulation by NGF indicative of neuroregeneration in capsaicin-treated rats

Intraplantar injections of human recombinant nerve growth factor (rhNGF-bet a) into the hind paw of capsaicin-treated adult rats are known to lead to a recovery of depleted peptide transmitter substances, to the immunohistoche mical reappearance of peptidergic innervation in the skin and in the dorsal horn of the spinal cord, as well as to a recovery of the function of capsa icin-lesioned neurons. In the present study a marker peptide for neuronal r egeneration and outgrowth, growth associated protein 43 (GAP-43), was inves tigated in lumbar dorsal root ganglia (DRCs) and in the hindpaw skin, in or der to differentiate which population of the sensory neurons responds with a neuroregenerative behaviour. In situ hybridization histochemistry (ISH) r evealed that at day 8 after the capsaicin treatment GAP-43 expression was s ignificantly increased in small DRG cells as compared to control animals, a nd treatment with NGF in capsaicinized rats lead to an even more pronounced increase of GAP-43 expression in the small-sized cell population. Intraepi dermal labelling of GAP-43 peptide was observed in the skin of control anim als, but was markedly reduced in the animals that were treated with capsaic in alone. However, intraepidermal GAP-43 immunoreactive (GAP-43-IR) fibres nearly fully recovered in the capsaicin + NGF-treated group. These results indicate that the population of small DRG cells shows spontaneous regenerat ive activity after a capsaicin lesion which does not lead to a successful r ecovery of nerve terminals in the skin. Only after an additional NGF treatm ent small DRG cells show an even stronger regenerative response which now a lso involves structural reorganization of neuron membranes and axogenesis i n the periphery. (C) 1999 Elsevier Science B.V. All rights reserved.