Abstract:Abstract Objective: To investigate the role of ten-eleven translocation (TET) protein TET2 in peripheral tissue inflammation and acute and chronic inflammatory pain. Methods: The expression and distribution of nerve fiber marker TUJ1 in plantar skin of wild-type (WT) and Tet2-/- mice was examined by immunofluorescence staining; Behavioral tests were used to detect the effect of knockout Tet2 gene on formalin- and complete Freund's adjuvant (CFA)-induced pain behavior and paw swelling; HE staining was used to detect the structure of plantar skin of WT and Tet2-/- mice at CFA 7d; Protein array was used to detect the differentially expressed inflammatory mediators in the paw of WT and Tet2-/- mice at CFA 7d. Results: Compared with WT mice, Tet2-/- mice showed normal distribution of plantar nerve fibers. Plantar injection of 0.5% formalin induced dual-phase spontaneous pain, which was more intense in Tet2-/- mice than that in WT mice. 50% CFA induced prolonged heat hyperalgesia and mechanical allodynia in WT and Tet2-/- mice, and pain sensitivity in Tet2-/- mice was more severe than that in WT mice. In Tet2-/- mice, 0.5% formalin and 50% CFA induced stronger plantar swelling than that in WT mice. The thickness of the dermis and hypodemis of the Tet2-/- mice was greater than that of WT mice at CFA 7d. Protein array showed that under the condition of inflammatory pain, knockout of Tet2 gene changed the expression of 104 inflammatory mediators, and 19 of them such as MMP9, resistin, and MMP3 were significantly up-regulated. Conclusion: Tet2 gene is involved in the regulation of pain. Knockout Tet2 gene induces an inflammatory response by releasing more inflammatory factors to enhance acute and chronic inflammatory pain. It indicated that Tet2 may play an anti-inflammatory and analgesic role in peripheral inflammatory pain.
