C-X-C Motif Chemokine Ligand 1 and its Receptor C-X-C Motif Chemokine Receptor 2 in Trigeminal Ganglion Contribute to Nerve Injury-Induced Orofacial Mechanical Allodynia

Objectives: This study aimed to investigate the exact role of CXCL1 and CXCR2 in the regulation of orofacial ectopic mechanical allodynia and their potential downstream mechanisms in the trigeminal ganglion (TG).
Methods: The head withdrawal threshold (HWT) of C57BL/6 mice was evaluated after inferior alveolar nerve (IAN) transection (IANX) and the effect of SB225002 (an inhibitor of CXCR2) on mechanical allodynia was examined. Then, the distribution and expression of CXCL1 and CXCR2 in the TG were further measured. To explore the potential downstream mechanism of CXCR2, the expression level of phosphor-PKC (p-PKC) and voltage-gated K⁺ (Kv) channels were checked after IANX and inhibition of CXCR2.
Results: IANX triggered persistent (>21 days) mechanical allodynia and upregulation of CXCL1 and CXCR2 in the TG. In addition, exogenous CXCL1 also lowered the HWT, which was alleviated by CXCR2 and protein kinase C (PKC) antagonists. In addition, IANX increased the phosphorylated PKC (p-PKC) levels and decreased the expression of voltage-gated potassium channels (Kv), and these effects were reversed by inhibition of CXCR2.
Conclusions: Our results demonstrated that CXCR2 participated in orofacial ectopic mechanical allodynia via downregulation of Kv1.4 and Kv1.1 through the PKC signaling pathway.