Peripheral Activation of Formyl Peptide Receptor 2/ALX by Electroacupuncture Alleviates Inflammatory Pain by Increasing Interleukin-10 Levels and Catalase Activity in Mice

by Selleckchem | Nov 17 2023

In the context of the electroacupuncture (EA) neurobiological mechanisms, we have previously demonstrated the involvement of formyl peptide receptor 2 (FPR2/ALX) in the antihyperalgesic effect of EA. The present study investigated the involvement of peripheral FPR2/ALX in the antihyperalgesic effect of EA on inflammatory cytokines levels, oxidative stress markers and antioxidant enzymes in an animal model of persistent inflammatory pain. Male Swiss mice underwent intraplantar (i.pl.) injection with complete Freund's adjuvant (CFA). Mechanical hyperalgesia was assessed with von Frey monofilaments. Animals were treated with EA (2/10 Hz, ST36-SP6, 20 minutes) for 4 consecutive days. From the first to the fourth day after CFA injection, animals received i.pl. WRW4 (FPR2/ALX antagonist) or saline before EA. Levels of inflammatory cytokines (TNF, IL-6, IL-4 and IL-10), antioxidant enzymes (catalase and superoxide dismutase), oxidative stress markers (TBARS, protein carbonyl, nitrite/nitrate ratio), and myeloperoxidase activity were measured in paw tissue samples. As previously demonstrated, i.pl. injection of the FPR2/ALX antagonist prevented the antihyperalgesic effect induced by EA. Furthermore, animals treated with EA showed higher levels of IL-10 and catalase activity in the inflamed paw, and these effects were prevented by the antagonist WRW4. EA did not change levels of TNF and IL-6, SOD and MPO activity, and oxidative stress markers. Our work demonstrates that the antihyperalgesic effect of EA on CFA-induced inflammatory pain could be partially associated with higher IL-10 levels and catalase activity, and that these effects may be dependent, at least in part, on the activation of peripheral FPR2/ALX.

Comments:

The study you've described investigates the mechanisms behind the antihyperalgesic (pain-reducing) effects of electroacupuncture (EA) in an animal model of persistent inflammatory pain. Here's a breakdown of the key findings and implications of the study:

1. **Experimental Setup**: Male Swiss mice were given intraplantar injections of complete Freund's adjuvant (CFA) to induce persistent inflammatory pain. Mechanical hyperalgesia (increased sensitivity to pain) was assessed using von Frey monofilaments. EA treatment was administered for four consecutive days, targeting specific acupuncture points (ST36-SP6) with specific parameters (2/10 Hz, 20 minutes per session). In addition to EA, some animals received intraplantar injections of WRW4, which is an antagonist of the formyl peptide receptor 2 (FPR2/ALX), before each EA session.

2. **Involvement of FPR2/ALX**: Previous research had already demonstrated that FPR2/ALX is involved in the antihyperalgesic effects of EA. This study confirmed this involvement by showing that blocking FPR2/ALX with the antagonist WRW4 prevented the antihyperalgesic effect induced by EA.

3. **Effects on Inflammatory Cytokines**: EA treatment led to increased levels of the anti-inflammatory cytokine interleukin-10 (IL-10) in the inflamed paw tissue. This suggests that the antihyperalgesic effect of EA may be associated with an increase in IL-10. However, EA did not significantly affect the levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-6 (IL-6).

4. **Effects on Antioxidant Enzymes**: EA treatment also resulted in increased catalase activity in the inflamed paw tissue. Catalase is an antioxidant enzyme that helps protect cells from oxidative stress. This finding suggests that the antihyperalgesic effect of EA may, in part, be mediated by an increase in catalase activity.

5. **Oxidative Stress and Other Markers**: EA did not significantly alter the levels of oxidative stress markers like TBARS (thiobarbituric acid-reactive substances) and protein carbonyl, nor did it affect superoxide dismutase (SOD) activity or myeloperoxidase (MPO) activity. These results indicate that the effects of EA on oxidative stress and other markers were relatively limited in this particular experimental setup.

6. **Peripheral FPR2/ALX Activation**: The study suggests that the observed effects on IL-10 levels and catalase activity may be at least partially dependent on the activation of peripheral FPR2/ALX, as blocking this receptor with WRW4 prevented these effects.

In summary, this study provides evidence that the antihyperalgesic effect of electroacupuncture in a model of persistent inflammatory pain may involve increased levels of the anti-inflammatory cytokine IL-10 and enhanced catalase activity in the inflamed tissue. These effects appear to be mediated, at least in part, by the activation of peripheral FPR2/ALX receptors. However, it's important to note that the study did not find significant effects on pro-inflammatory cytokines or other markers of oxidative stress.