Background & Aims

Type 1 interferon (IFN), including IFN-? and IFN-ß, demonstrates pain relief in addition to its antiviral properties. Increased miR-29a levels during inflammatory pain were found in a previous study. Since the Type 1 IFN receptor (IFNR1) is a target gene of miR-29a, we investigated the roles and mechanisms of miR-29a, type 1 IFN, and IFNR1 in inflammatory pain.

Methods

miR-29a assay, western blot for IFN-? and IFNR1 analysis were examined after behavioral tests on the 2nd, 3rd, 5th, 7th, and 10th days after injecting complete Freund’s adjuvant (CFA). Male rats received PEI, 4 nmole scrambled miRNA, 2 nmole miR-29a inhibitor and 4 nmole miR-29a inhibitor separately 5 days after injection of CFA. All rats’ spinal cord dorsal horns were dissected for performing western blot of IFNR1, p-ERK, ERK, and interferon-stimulated gene 15 (ISG15). Male rats received 4 nmole miR-29a mimic followed by injection of DMSO or 30 ug p-ERK antagonist (ASN007) 1h later. After the behavioral test, the spinal cord dorsal horn of 4 groups was dissected for performing western blot of p-ERK, ERK and IFNR1.

Results

Significant findings included elevated miR-29a (p < 0.001, n=6) and reduced IFNR1 levels (p = 0.004, n=6) from the 3rd to the 5th day in complete Freund's adjuvant (CFA)-induced inflammatory pain. IFN-ß levels began rising on the 2nd day post-CFA injection(p ? 0.01, n=6). By the fifth day, intrathecal administration of a miR-29a inhibitor alleviated CFA-induced mechanical allodynia and thermal hyperalgesia (p < 0.001, n=9). This intervention increased IFNR1 and interferon-stimulated gene (ISG)15 expression while reducing p-ERK levels (p < 0.001, n=9). Intriguingly, in naive rats, intrathecal injection of miR-29a mimics induced mechanical allodynia, reversed by an ERK antagonist (p < 0.001, n=6). This correlated with lower IFNR1 levels and elevated p-ERK in the spinal cord (p < 0.001, n=6).

Conclusions

Inhibiting miR-29a expression could alleviate inflammatory pain by upregulating IFNR1 and ISG 15 while suppressing p-ERK. The concerted actions of miR-29a and IFN-? play a crucial role in modulating CFA-induced inflammatory pain by regulating the expression of IFNR1, ISG 15, and p-ERK.

References

1.Sättler MB, Demmer I, Williams SK, et al. Effects of interferon-beta-1a on neuronal survival under autoimmune inflammatory conditions. Exp Neurol. 2006;201(1):172-181.
2.Hecker M, Thamilarasan M, Koczan D, et al. MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients. Int J Mol Sci. 2013;14(8):16087-16110.

Presenting Author

Ping Heng Tan

Poster Authors

Ping-Heng Tan

MD

Chi Mei Medical Center

Lead Author

Chien-Cheng Liu

Department of Anesthesiology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.

Lead Author

Yu-Yu Li

Department of Anesthesiology, Chi-Mei Medical Center, Chiali, Tainan, Taiwan

Lead Author

Topics

  • Mechanisms: Biological-Molecular and Cell Biology