Itch And Pain Sensation In A Murine Model Of Allergic Contact Dermatitis

Aims: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,the therapeutic effect is unsatisfactory due to its pathophysiological complexity.In this study,we aimed to identify crucial proteins involved in the nociceptive sensation of ACD.Main Methods:Based on a chemical-induced ACD murine model,we collected trigeminal ganglions from ACD and control group,and quantitative tandem mass tag(TMT)-labeling proteomic analysis was performed.The accuracy of bioinformatic analysis was further validated by immunohistochemistry.Key findings:A total of 7685 proteins were identified and analyzed.64 proteins were significantly upregulated,and 75 proteins were downregulated in ACD mice.GO analysis demonstrated that the changed proteins significantly enriched in terms related to immune process and peptidase activity in ACD mice.Proteins involved in Complement and coagulation cascades were notably changed in KEGG enrichment analysis.The upregulation of Complement 3 in trigeminal satellite cells of ACD mice was further confirmed by immunohistochemistry.ACD upregulated Complement 3 in trigeminal satellite cells.Conclusions:The complement system in sensory ganglion might play an important role in the formation of pruritic and nociceptive sensation in ACD.Objective:Allergic contact dermatitis(ACD)is a skin inflammatory disease manifested with itch and pain symptoms 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.In this study,we aimed to explore the role of CXCL12/CXCR4 signaling in a murine model of allergic contact dermatitis.Methods:Based on a chemical-induced ACD murine model,we collected trigeminal ganglions of ACD,Sen,and control mice for Western-blotting,Immunohistochemistry,and Immunofluorescence staining to investigate the effects of CXCL12/CXCR4 signaling on pain and itching associated with ACD.Results: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 the 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.Conclusions:Our findings suggested that blockade of the CXCL12/CXCR4 signaling pathway might be beneficial to relieve itch and pain sensation accompanying allergic contact dermatitis.