AUTHOR=Omura Carlos Minoru , Lüdtke Daniela Dero , Horewicz Verônica Vargas , Fernandes Paula Franson , Galassi Taynah de Oliveira , Salgado Afonso Shiguemi Inoue , Palandi Juliete , Baldança Heloiza dos Santos , Bittencourt Edsel B. , Mack Josiel Mileno , Seim Lynsey A. , Martins Daniel Fernandes , Bobinski Franciane TITLE=Decrease of IL-1β and TNF in the Spinal Cord Mediates Analgesia Produced by Ankle Joint Mobilization in Complete Freund Adjuvant-Induced Inflammation Mice Model JOURNAL=Frontiers in Physiology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.816624 DOI=10.3389/fphys.2021.816624 ISSN=1664-042X ABSTRACT=Objective

This study aims to investigate the effects of ankle joint mobilization (AJM) on mechanical hyperalgesia and peripheral and central inflammatory biomarkers after intraplantar (i.pl.) Complete Freund’s Adjuvant (CFA)-induced inflammation.

Methods

Male Swiss mice were randomly assigned to 3 groups (n = 7): Saline/Sham, CFA/Sham, and CFA/AJM. Five AJM sessions were carried out at 6, 24, 48, 72, and 96 h after CFA injection. von Frey test was used to assess mechanical hyperalgesia. Tissues from paw skin, paw muscle and spinal cord were collected to measure pro-inflammatory (TNF, IL-1β) and anti-inflammatory cytokines (IL-4, IL-10, and TGF-β1) by ELISA. The macrophage phenotype at the inflammation site was evaluated by Western blotting assay using the Nitric Oxide Synthase 2 (NOS 2) and Arginase-1 immunocontent to identify M1 and M2 macrophages, respectively.

Results

Our results confirm a consistent analgesic effect of AJM following the second treatment session. AJM did not change cytokines levels at the inflammatory site, although it promoted a reduction in M2 macrophages. Also, there was a reduction in the levels of pro-inflammatory cytokines IL-1β and TNF in the spinal cord.

Conclusion

Taken together, the results confirm the anti-hyperalgesic effect of AJM and suggest a central neuroimmunomodulatory effect in a model of persistent inflammation targeting the pro-inflammatory cytokines IL-1β and TNF.