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Allergic contact dermatitis (ACD) is a common inflammatory dermatosis characterized by persistent itch and pain after topical contact with reactive chemicals. Although it has been long recognized as a type-IV hypersensitivity, its complexity of pathophysiology mechanism makes it still a clinical aporia in treatment. In this study, we aimed to identify crucial proteins involved in the nociceptive sensation of ACD. Based on a chemical-induced ACD murine model, we collected trigeminal ganglions of ACD and control mice for quantitative tandem mass tag (TMT)-labeling proteomic analysis. Immunohistochemistry was further practiced to validate the bioinformatic analysis. A total of 7685 proteins were identified and analyzed. Sixty-four proteins were significantly upregulated, and 75 proteins were downregulated in ACD mice. GO analysis demonstrated that the changed proteins were significantly enriched in terms of immune and peptidase activity in ACD mice. Proteins involved in the complement and coagulation cascades were notably changed in the KEGG enrichment analysis. The upregulation of complement component 3 (C3) in trigeminal satellite cells of ACD mice was further confirmed by immunohistochemistry. ACD upregulated C3 in trigeminal satellite cells. The complement system in sensory ganglion might play an essential role in forming pruritic and nociceptive sensations in ACD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Allergic contact dermatitis is a skin inflammatory disease manifested with itch and pain symptom around the inflamed area. Chemokines such as CXCL12 are involved in the pathophysiology of allergic contact dermatitis, but little has been known about the effect of CXCL12/CXCR4 signaling for nociceptive sensation accompanying allergic contact dermatitis. Our study showed that CXCL12 and CXCR4 were upregulated in trigeminal ganglion with the progression of allergic contact dermatitis through western blotting and immunofluorescence. CXCL12 and CXCR4 were mainly upregulated in small-diameter neurons, which were co-localized with nociceptive markers in trigeminal ganglion. CXCR4 and CXCL12 were also expressed in trigeminal ganglion neurons retrograded from the skin lesion. Intradermal injection of CXCL12 enhanced the itch- and pain-like behavior which could be relieved by AMD3100, a CXCR4 antagonist, without changes of mast cells. Our findings suggested that blockade of CXCL12/CXCR4 signaling pathway might be beneficial to relieve itch and pain sensation accompanying allergic contact dermatitis.