Abstract
Inflammation of the cutaneous orofacial tissue can lead to a prolonged alteration of neuronal and nonneuronal cellular functions in trigeminal nociceptive pathways. In this study, we investigated the effects of experimentally induced skin inflammation by dithranol (anthralin) on macrophage activation in the rat trigeminal ganglion. Tissue localization and protein expression levels of ionized calcium-binding adaptor molecule 1 (Iba1), a macrophage/microglia-specific marker, and proliferation/mitotic marker antigen identified by the monoclonal antibody Ki67 (Ki67), were quantitatively analyzed using immunohistochemistry and western blots in control, dithranol-treated, dithranol- and corticosteroid-treated, and corticosteroid-treated trigeminal ganglia. Chronic orofacial dithranol treatment elicited a strong pro-inflammatory effect in the ipsilateral trigeminal ganglion. Indeed, daily dithranol treatment of the orofacial skin for 3–5 days increased the number of macrophages and Iba1 protein expression in the maxillary subregion of the ipsilateral ganglion. In the affected ganglia, none of the Iba1-positive cells expressed Ki67. This absence of mitotically active cells suggested that the accumulation of macrophages in the ganglion was not the result of resident microglia proliferation but rather the extravasation of hematogenous monocytes from the periphery. Subsequently, when a 5-day-long anti-inflammatory corticosteroid therapy was employed on the previously dithranol-treated orofacial skin, Iba1 immunoreactivity was substantially reduced in the ipsilateral ganglion. Collectively, our findings indicate that both peripheral inflammation and subsequent anti-inflammatory therapy affect macrophage activity and thus interfere with the functioning of the affected sensory ganglion neurons.
Highlights
Microglial cells belong to the monocyte/macrophage lineage (Kreutzberg 1996; Prinz et al 2011) and constitute an ontogenetically distinct population in the mononuclear phagocyte system (Ginhoux et al 2010)
We demonstrated that dithranol treatment transsynaptically downregulates the gene expression of the intracellular calcium-binding protein calmodulin (CaM) in rat principal sensory and motor trigeminal nuclei, in which altered amounts of CaM mRNA were observed in response to the treatment (Orojan et al 2008)
We investigated whether the induction of chronic orofacial inflammation by dithranol or a subsequent corticosteroid treatment resulted in an altered macrophage activity in the trigeminal ganglion
Summary
Microglial cells belong to the monocyte/macrophage lineage (Kreutzberg 1996; Prinz et al 2011) and constitute an ontogenetically distinct population in the mononuclear phagocyte system (Ginhoux et al 2010). In response to neural injuries, infections, or inflammation, microglia become activated, displaying a number of characteristic morphological, molecular, immunological, and functional changes (Kreutzberg 1996; Kettenmann et al 2011; Salter and Beggs 2014). This transformation parallels microglial proliferation, and homing and adhesion to damaged cells (Streit et al 1999). We investigated whether the induction of chronic orofacial inflammation by dithranol or a subsequent corticosteroid treatment resulted in an altered macrophage activity in the trigeminal ganglion. Our findings draw attention to the possibility that chronic peripheral inflammation, or antiinflammatory treatment, could affect neuronal functioning in the trigeminal ganglion via macrophage activation
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