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Medical Research

Effects of Auricular Stimulation on Inflammatory Parameters: Discussion of Findings

Kristen Sparrow • March 16, 2025

This is a more thorough discussion of this blog post.  Hua, K., Cummings, M., Bernatik, M., Brinkhaus, B., Usichenko, T., Willich, S. N., Scheibenbogen, C., & Dietzel, J. (2025). Effects of Auricular Stimulation on Inflammatory Parameters: Results of a Systematic Review and Meta-Analysis of Randomized Controlled Trials. Neuromodulation: Technology at the Neural Interface. https://doi.org/10.1016/j.neurom.2024.12.007

Abstract

Background

The number of randomized controlled trials (RCTs) using auricular stimulation (AS) techniques, such as transauricular vagus nerve stimulation, auricular electrostimulation, auricular acupuncture, and acupressure in experimental and clinical settings has increased markedly over the last three decades. This systematic review evaluates the effects of AS on biomarkers of inflammation and stress responses.

Materials and Methods

The following data bases were searched: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, and Scopus Data base. Data collection and analysis were conducted independently by two reviewers. Quality and risk assessments of the included studies were performed, and a meta-analysis of the effects of the most frequently assessed biomarkers was conducted using RevMan statistical software.

Results

A total of 1122 patients and healthy volunteers from 27 RCTs were included in this systematic review; 81% of the participants were female, with a median age of 51 years. Pooled data of 18 studies showed a significant effect of AS regarding a reduction of serum C-reactive protein, tumor necrosis factor-α, interleukin (IL)-6, and IL-10. Although IL-4, IL1β, cortisol, substance P and calcitonin gene-related peptide, and adrenocorticotropic hormone did not show any changes, salivary amylase increased under AS.

Conclusions

The influence of inflammatory cytokines seems to be mediated by AS. More research is needed to investigate the effects of AS on the immunologic system in addition to its clinical significance in high-quality RCT.

Here are the five main points from the article on auricular stimulation and inflammation, including its potential for future therapy:

  1. Auricular Stimulation (AS) Modulates Inflammatory Biomarkers
    The systematic review and meta-analysis of 27 randomized controlled trials (RCTs) showed that AS techniques (e.g., auricular acupuncture, electrostimulation, and transauricular vagus nerve stimulation) significantly reduced key inflammatory markers such as C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-10. However, some biomarkers like IL-4, IL-1β, and cortisol did not show significant changes.
  2. Mechanism of Action through the Vagus Nerve
    AS is believed to stimulate the auricular branch of the vagus nerve (ABVN), triggering the body’s anti-inflammatory response via the autonomic nervous system. This mechanism is similar to the well-documented vagus nerve-mediated anti-inflammatory pathways seen in other neuromodulation therapies.
  3. Potential Applications in Chronic and Acute Inflammatory Conditions
    The reduction in inflammatory cytokines suggests AS could be useful for conditions linked to chronic inflammation, such as cardiovascular disease, rheumatoid arthritis, and post-surgical recovery. Trials also indicated possible benefits for managing post-operative inflammation, stress-induced inflammation, and autoimmune diseases.
  4. Emerging Clinical Significance and Research Needs
    Although the results are promising, more high-quality clinical trials are needed to determine AS’s full potential in medical practice. Future studies should focus on specific inflammatory diseases, standardizing stimulation protocols, and comparing AS effects on different patient populations.
  5. Therapeutic Potential and Future Directions
    AS could be an accessible, non-invasive alternative for inflammation-related conditions, potentially reducing reliance on pharmaceuticals. Given its relatively low risk of adverse effects, it may serve as a complementary treatment for managing stress, pain, and systemic inflammation. However, further research is required to optimize its clinical application and fully understand its long-term effects.

Key Inflammatory Biomarkers Affected by AS

The study analyzed multiple biomarkers related to inflammation and the stress response. Some showed significant changes, while others remained unchanged.

1. Significant Reductions in Inflammatory Markers

Meta-analysis of 18 trials found that AS significantly reduced the following inflammatory biomarkers:

  • C-Reactive Protein (CRP)
    • A widely used marker of systemic inflammation, CRP was significantly reduced in AS-treated groups compared to controls.
    • One study involving post-lung surgery patients showed that those receiving AS had lower CRP levels (90 mg/L ± 42) compared to the control group (157 mg/L ± 83, p = 0.01).
    • This suggests AS could play a role in post-surgical recovery by reducing inflammatory responses.
  • Tumor Necrosis Factor-Alpha (TNF-α)
    • A major pro-inflammatory cytokine involved in systemic inflammation and immune regulation.
    • Seven studies analyzed TNF-α levels, with pooled data showing a marginally significant reduction (Standardized Mean Difference (SMD) = -0.46, 95% CI [-0.91 to 0.00], p = 0.05).
    • Some studies showed stronger results: One study in patients with atrial fibrillation (AF) found that TNF-α decreased by 23% in the AS group compared to the control (p = 0.0093).
  • Interleukin-6 (IL-6)
    • A cytokine involved in inflammation and immune response, often elevated in chronic diseases.
    • AS significantly reduced IL-6 levels (SMD = -0.57, 95% CI [-0.98 to -0.15], p = 0.007).
    • In one trial involving rheumatoid arthritis patients, IL-6 was reduced by 27% after AS compared to baseline.
  • Interleukin-10 (IL-10)
    • An anti-inflammatory cytokine that plays a role in immune regulation.
    • Meta-analysis found significant reductions in IL-10 following AS (SMD = -0.37, 95% CI [-0.66 to -0.09], p = 0.01).
    • However, reductions in IL-10 may reflect a broader modulation of immune function rather than a purely anti-inflammatory effect.

2. No Significant Changes in Some Biomarkers

Not all inflammatory and stress-related markers showed changes with AS:

  • Interleukin-1β (IL-1β): Showed a nonsignificant trend toward reduction.
  • Interleukin-4 (IL-4): No significant difference between AS and control groups.
  • Cortisol: Despite being a stress-related hormone, AS did not significantly reduce cortisol levels across studies.
  • Substance P and Calcitonin Gene-Related Peptide (CGRP): No significant effects, suggesting AS does not directly influence these neuropeptides involved in pain signaling.

3. Increase in Salivary Amylase

Interestingly, salivary amylase levels increased in participants undergoing AS. Salivary amylase is a marker of sympathetic nervous system activation and stress response. The significance of this finding remains unclear, as AS is generally associated with vagal (parasympathetic) activation.

Implications of These Findings

  • The reductions in CRP, TNF-α, IL-6, and IL-10 suggest that AS may exert anti-inflammatory effects through neuromodulation of the autonomic nervous system, specifically via vagal nerve stimulation.
  • These results indicate potential applications for chronic inflammatory diseases, postoperative recovery, and stress-related conditions.
  • However, the effects appear to be cytokine-specific, meaning AS does not broadly suppress all inflammatory markers but may regulate immune function in a more targeted way.

Comparing the effects of Auricular Stimulation (AS) with Manual Acupuncture (MA) and Electroacupuncture (EA) on inflammatory biomarkers reveals both shared and distinct outcomes.

1. Reduction of Pro-Inflammatory Cytokines

  • Tumor Necrosis Factor-Alpha (TNF-α):
    • Auricular Stimulation (AS): Studies indicate that AS can lead to a significant reduction in TNF-α levels.
    • Manual and Electroacupuncture (MA and EA): Both MA and EA have been shown to significantly decrease TNF-α concentrations. Notably, EA demonstrated a more pronounced reduction compared to MA. citeturn0search1
  • Interleukin-1β (IL-1β):
    • Auricular Stimulation (AS): The impact of AS on IL-1β levels appears to be minimal or non-significant.
    • Manual and Electroacupuncture (MA and EA): Both modalities have been associated with significant reductions in IL-1β levels. citeturn0search1

2. Modulation of Anti-Inflammatory Cytokines

  • Interleukin-10 (IL-10):
    • Auricular Stimulation (AS): Research indicates that AS can significantly reduce IL-10 levels.
    • Manual and Electroacupuncture (MA and EA): The effects of MA and EA on IL-10 were not specifically highlighted in the referenced studies.
  • Interleukin-13 (IL-13):
    • Auricular Stimulation (AS): The influence of AS on IL-13 levels has not been prominently reported.
    • Manual and Electroacupuncture (MA and EA): Both MA and EA treatments have been shown to significantly increase IL-13 levels, suggesting an enhancement of anti-inflammatory responses. citeturn0search1

3. Impact on Cartilage Degradation Biomarkers

  • Matrix Metalloproteinases (MMP-3 and MMP-13):
    • Auricular Stimulation (AS): There is limited data on the effects of AS on cartilage degradation biomarkers such as MMP-3 and MMP-13.
    • Manual and Electroacupuncture (MA and EA): Both MA and EA have been associated with significant reductions in MMP-3 and MMP-13 levels, indicating a potential protective effect against cartilage degradation. citeturn0search1

4. Comparative Efficacy Between EA and MA

While both EA and MA positively influence inflammatory markers, EA may offer a more substantial reduction in certain pro-inflammatory cytokines, such as TNF-α. However, overall differences between the two modalities are not consistently significant across all biomarkers. citeturn0search1

5. Mechanistic Insights

The anti-inflammatory effects observed with both AS and acupuncture techniques are believed to be mediated through modulation of the autonomic nervous system, particularly via vagal nerve activation. This activation can influence systemic inflammation and immune responses. citeturn0search6

Conclusion

Both Auricular Stimulation and traditional acupuncture methods (Manual and Electroacupuncture) demonstrate potential in modulating inflammatory responses. While EA may provide a more pronounced effect on certain pro-inflammatory markers, the choice of modality should consider individual patient conditions, treatment goals, and practitioner expertise.