Cellular pathology changes in rat skin following intradermal injection of nerve growth factor: neutrophil-dependent and -independent events

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Abstract
Nerve growth factor (NGF) regulates the survival and development of specific populations of neurones and is involved in wound healing. A further area of study relating to the role of neurotrophins in the mature animal has concerned the possibility that NGF may be a pivotal mediator of inflammation and pain. It has previously been shown that injection of intradermal NGF can result in a neutrophil-dependent hyperalgesia in the rat. The purpose of the present study was to examine the pathological consequence of NGF injected intradermally into mature rat skin and to examine further the role of neutrophils. Standard histopathology techniques (H & E) were employed to determine inflammatory cell counts. Circulating neutrophils were depleted using an anti-rat neutrophil antiserum and results were compared to treatment with vehicle controls. Saline-pretreated rats exhibited normal circulating neutrophil numbers and the dorsal skin showed a significant increase of neutrophil and macrophages at 3 and 5 h and lymphocytes at 5 h after NGF treatment. By comparison, skin sites from neutrophil-depleted rats did not demonstrate a significant increase in neutrophil and macrophage accumulation after NGF administration. All NGF-treated sites, independent of pretreatment, demonstrated abnormal muscle fibre morphology and proliferation of the muscle sarcolemmal nuclei after NGF injection, indicative of tissue injury. In addition, oedema and some fibroplasia were also noted. Furthermore, fibrin production was increased at 3 and 5 h after NGF administration. It is suggested that NGF has a damaging effect on rat muscle which is independent of accumulating neutrophil and other inflammatory cells. In conclusion, the findings indicate a link between NGF-induced neutrophil and macrophage accumulation, as the increase in dermal macrophages was not observed in neutrophil-depleted rats. The results also suggest that NGF can have a profound effect on rat muscle and that this effect may be related to muscle regeneration. Copyright © 2002 John Wiley & Sons, Ltd.