Skin homeostasis during inflammation, a role for nerve growth factor

Abstract

The skin is a neuroendocrine immune organ in which many different molecules operate in autocrineparacrine manner to guarantee tissue homeostatsis in physiological and pathophysiological conditions. In this paper we examined NGF and p75 receptor expression in the skin, during CFA induced inflammation, in a timecourse study. We also examined cutaneus innervation and proliferation, by means of immunohistochemistry and quantitative image analysis, RT-PCR and Western blot. Spontaneous and evoked pain-behavior was also measured in experimental rats. The main results can be summarized as follows: 1). a peripheral sensory neuropathy develops in this condition, as indicated by thermal hyperalgesia, thus leading to a sensory denervation of the hind-paw skin as indicated by disappearance of CGRP and PGP9.5-IR fibers; 2). NGF and p75 expression (mRNA and protein) increases in the skin (keratinocytes) in the acute phase of CFA inflammation; 3). at this stage, a higher proliferative activity is observed in the skin, as defined by the expression of cell cycle-associated protein Ki67; 4). in the long-lasting chronic phase there is a further upregulation of NFG and p75 expression in the skin; 5). trkA mRNA expression inversely correlates with p75 and NGF mRNA expression. These results suggest that CFA chronic inflammation evolves from inflammation to a small fibers sensory neuropathy and NGF seems to play a role in both events.