Abstract
Orofacial pain (OFP) is a clinically very common and the most troubling condition; however, there is few effective way to relieve OFP. Rab11a, a small molecule guanosine triphosphate enzyme, is one of the Rab member family playing a vital role in intracellular endocytosis and the pain process. Therefore, we investigated the hub genes of rat OFP model induced by Complete Freund's Adjuvant (CFA) via re-analyzing microarray data (GSE111160). We found that Rab11a acted as a key hub gene in the process of OFP. During the validation of Rab11a, the OFP model was established by peripheral injection of CFA, which decreased the head withdrawal threshold (HWT) and head withdrawal lantency (HWL). Rab11a was observed in NeuN of Sp5C instead of GFAP/IBA-1, and double-IF of Rab11a and Fos positive cells were increased on the 7th day after CFA modeling statistically. Rab11a protein expression in TG and Sp5C of CFA group was also significantly increased. Interestingly, injection of Rab11a-targeted short hairpin RNA (Rab11a-shRNA) into Sp5C could reverse the decrease in HWT and HWL and reduce the expression level of Rab11a. Electrophysiological recording further demonstrated that the activity of Sp5C neuron was improved in CFA group, while Rab11a-shRNA considerably decreased the enhancement of Sp5C neuronal activity. Finally, we detected the expression level of p-PI3K, p-AKT, and p-mTOR in Sp5C of rats after injecting the Rab11a-shRNA virus. To our surprise, CFA upregulated the phosphorylation of PI3K, AKT and mTOR in Sp5C, and Rab11a-shRNA downregulated these molecules' expression. Our data suggest that CFA activates the PI3K/AKT signaling pathway through up-regulating Rab11a expression, which can induce OFP hyperalgesia development furtherly. Targeting Rab11a may be a novel treatment strategy for OFP.