In conclusion, we explored the roles and relationship of CB1R and HCN2 in CM and paid close attention to the role of the HCN2-pNR2B signal in the CB1R-mediated regulatory mechanism of central sensitization in CM (Fig. 12), which helps to further identify CB1R as a promising candidate for future prevention of CM. This evidence concerns the gene HCN2 and cutaneous mastocytosis.