To evaluate the feasibility, safety, and potential therapeutic effects of percutaneous sacral nerve stimulation (SNS) via acupuncture needles in patients with active rheumatoid arthritis (RA), and to explore its modulatory effects on autonomic nervous system function.

This was a randomized, double-blind, sham-controlled pilot study conducted at Nanjing First Hospital from May 2021 to May 2023. Thirty patients with active RA were screened, and 24 were enrolled. Inclusion criteria included: age 18-65 years; meeting the 2010 ACR/EULAR RA classification criteria; and mild-to-moderate active disease with DAS28-ESR between 3.2 and 5.1. Patients were randomly allocated to receive either active SNS (n=11) or sham stimulation (n=10) for 14 consecutive days. In the SNS group, sterile silver needles were inserted into the Zhongliao (BL-33) and Xialiao (BL-34) acupoints, corresponding to the S3 and S4 sacral nerves via the posterior sacral foramina. The sham group received superficial needle insertion at sites 8-10 cm lateral to the true acupoints. Both groups received electrical stimulation with identical parameters: 5 Hz frequency, 0.5 ms pulse width, 10-second on/90-second off cycle, and 0.5 mA intensity, for 60 minutes daily. Primary outcomes included changes in tender joint count (TJC), swollen joint count (SJC), pain visual analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Disease Activity Score in 28 joints (DAS28). Secondary outcomes comprised: (1) patient-reported outcomes including Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS); (2) serum inflammatory cytokines (IL-1β, IL-2, IL-6, IL-10, IL-11, IL-17, IL-18, TNF-α, IFN-γ, GM-CSF) measured by ELISA; and (3) heart rate variability (HRV) parameters as indicators of autonomic function. All assessments were performed at baseline and after the 2-week intervention.

Twenty-one patients completed the trial (87.5% retention rate). Baseline characteristics were comparable between groups, although the SNS group had significantly higher VAS scores (6.3±1.2 vs. 4.9±1.4, P=0.024). After 14 days of treatment, the SNS group demonstrated significant within-group improvements in TJC (P<0.05), VAS pain score (P<0.05), DAS28-ESR (P<0.05), and DAS28-CRP (P<0.05), whereas no significant changes were observed in the sham group. No significant between-group differences were found for SJC, ESR, or CRP. Regarding functional and psychological outcomes, no significant post-treatment differences were observed between groups in HAQ-DI, FACIT-F, SAS, or SDS scores. Serum cytokine analysis revealed no significant changes in any of the ten measured cytokines in either group, although the SNS group showed downward trends for IL-2 (P=0.300) and TNF-α (P=0.336). Notably, HRV analysis demonstrated a statistically significant increase in rMSSD (root mean square of successive differences between adjacent NN intervals)—a primary marker of parasympathetic activity—exclusively in the SNS group (P<0.05). No significant changes were observed in other HRV parameters including SDNN, SDANN, SDNN index, or pNN50 in either group. The intervention was well-tolerated with minimal adverse events: transient skin pain during needle insertion was reported by a minority of patients, and one case of minor bruising resolved within one week. No serious adverse events were documented.

Non-invasive SNS represents a promising, novel neuromodulatory approach for active RA, demonstrating clinically meaningful improvements in disease activity and pain with a plausible autonomic mechanism. These preliminary findings warrant further rigorous investigation.