Interferon-β suppresses inflammatory pain through activating µ-opioid receptor

Author:

Liu Chien Cheng1ORCID,Lu I Cheng2,Wang Li Kai34ORCID,Chen Jen Yin4,Li Yu Yu4,Yang Chih Ping4,Liu Ping Hsin1,Cheng Wan Jung4,Tan Ping Heng4

Affiliation:

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

2. Department of Anesthesiology, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan

3. Southern Taiwan University of Science and Technology, Tainan City, Taiwan

4. Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan

Abstract

Interferons (IFNs) are cytokines secreted by infected cells that can interfere with viral replication. Besides activating antiviral defenses, type I IFNs also exhibit diverse biological functions. IFN-β has been shown to have a protective effect against neurotoxic and inflammatory insults on neurons. Therefore, we aimed to investigate the possible role of IFN-β in reducing mechanical allodynia caused by Complete Freund’s Adjuvant (CFA) injection in rats. We assessed the antinociceptive effect of intrathecal IFN-β in naïve rats and the rats with CFA–induced inflammatory pain. After the behavioral test, the spinal cords of the rats were harvested for western blot and immunohistochemical double staining. We found that intrathecal administration of IFN-β in naïve rats can significantly increase the paw withdrawal threshold and paw withdrawal latency. Further, the intrathecal injection of a neutralizing IFN-β antibody can reduce the paw withdrawal threshold and paw withdrawal latency, suggesting that IFN-β is produced in the spinal cord in normal conditions and serves as a tonic inhibitor of pain. In addition, intrathecal injection of IFN-β at dosages from 1000 U to 10000 U demonstrates a significant transient dose-dependent inhibition of CFA-induced inflammatory pain. This analgesic effect is reversed by intrathecal naloxone, suggesting that IFN-β produces an analgesic effect through central opioid receptor-mediated signaling. Increased expression of phospho-µ-opioid receptors after IFN-β injection was observed on western blot, and immunohistochemical staining showed that µ-opioids co-localized with IFN-α/βR in the dorsal horn of the spinal cord. The findings of this study demonstrate that the analgesic effect of IFN-β is through µ-opioid receptors activation in spial cord.

Funder

E-Da Hospital Grants

Chi Mei Hospital Grants

Taiwan Ministry of Science and Technology Grants

Publisher

SAGE Publications

Subject

Anesthesiology and Pain Medicine,Cellular and Molecular Neuroscience,Molecular Medicine

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