CXCL12/CXCR4 signaling induced itch and pain sensation in a murine model of allergic contact dermatitis

Abstract

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.

Exploring the Association between Rosacea and Acne by Integrated Bioinformatics Analysis

“…Helfrich et al found an 8-fold increase in CXCR4 expression in lesional skin from ETR patients compared to HC 51 . Su et al demonstrated that in the mouse model of allergic contact dermatitis, the CXCL12/CXCR4 signaling pathway induces itching and pain feeling 52 . It requires further study to determine whether the CXCL12/CXCR4 signaling pathway has a role in some rosacea and acne patients with itching and pain.…”

CXCR4/CXCL12 axis: “old” pathway as “novel” target for anti‐inflammatory drug discovery

“…CXCL12 activates TG by binding to CXCR4, thereby exacerbating pain and itching caused by inflammation. 143 Collectively, numerous reports have shown that CXCR4 antagonists can be used to improve and prevent skin inflammation. A natural fragment of serum albumin, named EPI-X4, has also been found to improve dermatitis.…”

“…TG contains a large number of pain afferent nerves, where neurons overexpress CXCR4 under ACD conditions. CXCL12 activates TG by binding to CXCR4, thereby exacerbating pain and itching caused by inflammation 143 …”

Neuroimmune communication regulating pruritus in atopic dermatitis

“…Intradermal injection of CXCL12 (1 mg/10 mL) enhanced the itch-scratching behavior, which was relieved by CXCR4 antagonism (AMD3100, 5 mg/kg). 164 The CXCL10/ CXCR3 axis contributes on a spinal cord level to chronic itch in mouse models of dry skin and allergic contact dermatitis. [165][166][167] Another chemokine, CCL2, can directly activate CCR2-expressing cutaneous small-diameter DRG neurons, resulting in itch-and pain-like behaviors.…”