Abstract
BACKGROUND: The therapeutic benefits of electroacupuncture (EA) for atopic dermatitis (AD) are recognized, yet the underlying mechanisms remain elusive. Given the side effects associated with clinical CB2 receptor (CB2R) agonists used in AD treatment, our study seeks to elucidate EA's role in modulating CB2R in lesional skin and its impact on antipruritic and anti-inflammatory responses using an AD mouse model. METHODS: The AD model was induced with MC903, and EA was applied to'Qu chi'(LI11) and'He gu'(LI4) acupoints, corresponding to the neck dermatome. Mice were assessed for scratching behavior and scoring atopic dermatitis score every other day. Immunohistochemistry and immunofluorescence evaluated epidermal thickness, inflammatory cell infiltration, and CB2R expression. Meanwhile, RT-qPCR detected the expression of inflammatory factors, their receptors, and cannabinoid metabolizing enzymes. The study used both wild-type and CB2R knockout (CB2R(-/-)) mice to clarify CB2R's role in EA's treatment of AD. RESULTS: EA treatment effectively mitigated chronic itching and AD-like symptoms, especially the proliferation of mast cells and CD4(+) T cells. Additionally, EA treatment was found to reduce the expression of IL4, IL13, and IL31 in the skin lesions, as well as the expression of their receptors IL4R and IL31R in the dorsal root ganglia of the neck, contributing to its anti-inflammatory action. Moreover, EA augmented the expression of CB2R and regulated endocannabinoid metabolic enzymes. Furthermore, using CB2R(-/-) mice, it was found that the antipruritic and anti-inflammatory effects of EA were impaired. EA inhibited ERK phosphorylation in lesional skin, which was also reversed in CB2R(-/-) mice. CONCLUSION: EA exerts therapeutic effects on persistent itch and skin inflammation in AD mice by activating CB2R, thereby inhibiting mast cell and CD4(+) T cell proliferation and the expression of associated inflammatory factors, as well as downstream ERK phosphorylation.