Objective To evaluate the feasibility and safety as well as potential effects of percutaneous sacral nerve stimulation (SNS) via acupuncture needles in patients with active rheumatoid arthritis (RA). Methods Twenty-one patients with active RA were allocated to receive either active SNS (n = 11) or sham stimulation (n = 10) for 60 min daily over 14 days. Primary outcomes were changes in disease activity, assessed by the Disease Activity Score in 28 joints (DAS-28), tender joint count (TJC), swollen joint count (SJC), pain intensity on a visual analogue scale (VAS), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Secondary outcomes included the following: (1) patient-reported outcomes for joint function, fatigue, anxiety, and depression; (2) serum levels of inflammatory cytokines; and (3) heart rate variability (HRV) parameters as a measure of autonomic function. Results In this pilot study, the SNS group showed significant within-group improvements in TJC, VAS, DAS28-ESR, and DAS28-CRP. However, an analysis of covariance (ANCOVA) adjusting for baseline values revealed no significant between-group differences in clinical and inflammatory parameters. The SNS group showed a significant increase in rMSSD (parasympathetic marker), with the between-group difference sustained after baseline adjustment. No significant differences were observed in functional and psychological scores or serum cytokine levels between the two groups. Conclusion This first-in-human study indicates that percutaneous SNS is feasible and safe, with a possible modulatory effect on autonomic function in active RA. Further large‑scale, adequately powered trials are warranted to confirm the clinical efficacy and mechanisms of SNS in RA. Trial registration This study was registered at ClinicalTrials.gov on March 25, 2021 under the identifier NCT04821050 (Protocol ID: 202002053).<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Key Points • First-in-human pilot study of percutaneous sacral nerve stimulation (SNS) in active RA. • SNS was associated with significant within-group improvements in tender joint count, pain VAS, and DAS28, but between-group differences did not reach statistical significance after baseline adjustment. • SNS significantly enhances parasympathetic activity (rMSSD) compared with sham stimulation, an effect that remained significant after adjusting for baseline differences. • Percutaneous SNS was safe and well-tolerated, with no serious adverse events reported. </entry> </row> </tbody> </tgroup> </Table>

Sacral nerve stimulation modulates disease activity and autonomic function in active rheumatoid arthritis: a randomized pilot study

期刊论文
发表日期：

2026年7月9日

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Xiaoqin Wang,
Bingguo Xu,
Guoxin Wang,
Leilei Yang,
Dinglei Su,
Jiande D. Z. Chen

摘要

Objective

To evaluate the feasibility and safety as well as potential effects of percutaneous sacral nerve stimulation (SNS) via acupuncture needles in patients with active rheumatoid arthritis (RA).

Methods

Twenty-one patients with active RA were allocated to receive either active SNS (n = 11) or sham stimulation (n = 10) for 60 min daily over 14 days. Primary outcomes were changes in disease activity, assessed by the Disease Activity Score in 28 joints (DAS-28), tender joint count (TJC), swollen joint count (SJC), pain intensity on a visual analogue scale (VAS), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Secondary outcomes included the following: (1) patient-reported outcomes for joint function, fatigue, anxiety, and depression; (2) serum levels of inflammatory cytokines; and (3) heart rate variability (HRV) parameters as a measure of autonomic function.

Results

In this pilot study, the SNS group showed significant within-group improvements in TJC, VAS, DAS28-ESR, and DAS28-CRP. However, an analysis of covariance (ANCOVA) adjusting for baseline values revealed no significant between-group differences in clinical and inflammatory parameters. The SNS group showed a significant increase in rMSSD (parasympathetic marker), with the between-group difference sustained after baseline adjustment. No significant differences were observed in functional and psychological scores or serum cytokine levels between the two groups.

Conclusion

This first-in-human study indicates that percutaneous SNS is feasible and safe, with a possible modulatory effect on autonomic function in active RA. Further large‑scale, adequately powered trials are warranted to confirm the clinical efficacy and mechanisms of SNS in RA.

Trial registration

This study was registered at ClinicalTrials.gov on March 25, 2021 under the identifier NCT04821050 (Protocol ID: 202002053).

Key Points

• First-in-human pilot study of percutaneous sacral nerve stimulation (SNS) in active RA.

• SNS was associated with significant within-group improvements in tender joint count, pain VAS, and DAS28, but between-group differences did not reach statistical significance after baseline adjustment.

• SNS significantly enhances parasympathetic activity (rMSSD) compared with sham stimulation, an effect that remained significant after adjusting for baseline differences.

• Percutaneous SNS was safe and well-tolerated, with no serious adverse events reported.