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Objectives: Trigeminal neuralgia (TN) is a common neuropathic pain. Voltage-gated potassium channel (Kv) has been confirmed to be involved in the occurrence and development of TN, but the specific mechanism is still unclear. MicroRNA may be involved in neuropathic pain by regulating the expression of Kv channels and neuronal excitability in trigeminal ganglion (TG). This study aims to explore the relationship between Kv1.1 and in TG with a TN model, evaluate whether has a regulatory effect on Kv1.1, and to provide a new target and experimental basis for the treatment of TN.
Methods: A total of 48 SD rats were randomly divided into 6 groups: 1) a sham group (=12), the rats were only sutured at the surgical incision without nerve ligation; 2) a sham+agomir NC group (=6), the sham rats were microinjected with agomir NC through stereotactic brain injection in the surgical side of TG; 3) a sham+ agomir group (=6), the sham rats were microinjected with agomir via stereotactic brain injection in the surgical side of TG; 4) a TN group (=12), a TN rat model was constructed using the chronic constriction injury of the distal infraorbital nerve (dIoN-CCI) method with chromium intestinal thread; 5) a TN+antagonist NC group (=6), TN rats were microinjected with antagonist NC through stereotactic brain injection method in the surgical side of TG; 6) a TN+ antagonist group (=6), TN rats were microinjected with antagonist through stereotactic brain injection in the surgical side of TG. The change of mechanical pain threshold in rats of each group after surgery was detected. The expressions of Kv1.1 and in the operative TG of rats were detected by Western blotting and real-time reverse transcription polymerase chain reaction. Dual luciferase reporter genes were used to determine whether there was a target relationship between Kv1.1 and and whether directly affected the 3'-UTR terminal of . The effect of brain stereotaxic injection was evaluated by immunofluorescence assay, and then the analogue of (agomir) and agomir NC were injected into the TG of rats in the sham group by brain stereotaxic apparatus to overexpress . The inhibitor (antagomir) and antagomir NC were injected into TG of rats in the TN group to inhibit the expression of . The behavioral changes of rats before and after administration were observed, and the expression changes of and Kv1.1 in TG of rats after intervention were detected.
Results: Compared with the baseline pain threshold, the facial mechanical pain threshold of rats in the TN group was significantly decreased from the 5th to 15th day after the surgery (<0.05), and the facial mechanical pain threshold of rats in the sham group was stable at the normal level, which proved that the dIoN-CCI model was successfully constructed. Compared with the sham group, the expression of mRNA and protein in TG of the TN group was down-regulated (both <0.05), and the expression of was up-regulated (<0.05). The results of dual luciferase report showed that the luciferase activity of rno- mimics and WT transfected with 6 nmol/L or 20 nmol/L were significantly decreased compared with those transfected with mimic NC and wild-type WT, respectively (<0.001). Compared with low dose rno- mimics (6 nmol/L) co-transfection group, the relative activity of luciferase in the high dose rno- mimics (20 nmol/L) cotransfection group was significantly decreased (<0.001). The results of immunofluorescence showed that drugs were accurately injected into TG through stereotaxic brain. After the expression of in the TN group, the mechanical pain threshold and the expression of mRNA and protein in TG were increased. After overexpression of in the sham group, the mechanical pain threshold and the expression of mRNA and protein in TG were decreased.
Conclusions: Both Kv1.1 and are involved in TN and can regulate Kv1.1 expression by binding to the 3'-UTR of KCNA1.
