Neurotrophic factor changes in the rat thick skin following chronic constriction injury of the sciatic nerve

We observed a decrease in peptidergic fiber innervation at 1 week after the application of a chronic constriction injury (CCI) to the sciatic nerve, followed by a recovery, correlating with TrkA protein levels. ProNGF expression in CCI animals was significantly higher than in sham-operated controls from 1-4 weeks post-CCI. ProNGF immunoreactivity was increased in mast cells at 1 week post-CCI and, at later time points, in keratinocytes. P75 expression within the dermis and epidermis was significantly higher in CCI-operated animals than in controls and these changes were localized to neuronal and non-neuronal cell populations using specific markers for each.We describe proNGF expression by non-neuronal cells over time after nerve injury as well as the association of NGF-responsive fibers to proNGF-expressing target tissues. ProNGF expression increases following nerve injury in those cell types previously suggested to express it.Nerve growth factor (NGF) is a 13 kDa neurotrophin [1]. Its roles within the peripheral nervous system include the maintenance of the adult sensory afferents and sympathetic post-ganglionic efferents [2,3]. During embryonic development, its expression is essential for the normal development and maturation of the sympathetic nervous system [4]. Mice engineered to over-express NGF in keratinocytes were associated with increased peptidergic fiber density as well as inappropriate innervation by sympathetic efferents [5,6]. These mice were also shown to have heightened sensitivity to applied heat and mechanical stimuli [7]. We have previously demonstrated that following nerve injury, there was an increase in sympathetic and peptidergic innervation in skin, comparable to that occurring following the overexpression of NGF [8-12]. We have also shown that an increase in sympathetic and peptidergic innervation occurs following application of nerve injury models [8-10]. These observed changes in NGF-responsive sympathetic and sensory fibers have been pro