This randomized clinical trial attempts to determine whether electroacupuncture reduces pain severity compared with sham electroacupuncture and evaluate its safety in patients with postherpetic neuralgia.
Key Points
Question
Does a 4-week course of electroacupuncture reduce pain intensity in adults with postherpetic neuralgia compared with sham electroacupuncture?
Findings
In this multicenter randomized clinical trial of 448 patients with postherpetic neuralgia, electroacupuncture reduced pain scores more than sham electroacupuncture at 4 weeks. Electroacupuncture also increased responder rates (≥30% reduction in pain scores), with benefits persisting at 1 month.
Meaning
Despite a modest mean pain score reduction, this 4-week course of electroacupuncture significantly improved responder rates; these findings suggest that electroacupuncture may have a role in multimodal management of postherpetic neuralgia.
Abstract
IMPORTANCE
Postherpetic neuralgia (PHN) is a refractory neuropathic pain condition with limited therapeutic options. Although electroacupuncture has demonstrated potential analgesic effects, high-quality evidence from rigorous randomized clinical trials remains limited.
OBJECTIVE
To determine whether electroacupuncture reduces pain severity compared with sham electroacupuncture and evaluate its safety in patients with PHN.
Design, Setting, and Participants
This multicenter, randomized, sham-controlled clinical trial took place at 7 tertiary hospitals in China and enrolled participants from October 2020 to July 2022, with the last follow-up in September 2022. Data analyses were performed from August to December 2025. Participants with PHN aged 45 to 75 years and moderate to severe pain (11-point Numeric Rating Scale [NRS-11] score ≥4) were recruited. Of 1072 patients screened, 624 were excluded. The remaining 448 participants were randomized to electroacupuncture (n = 225) or sham electroacupuncture (n = 223); 383 participants (85.49%) completed the trial.
INTERVENTION
Twenty sessions of electroacupuncture or sham electroacupuncture over 4 weeks, followed by a 4-week posttreatment follow-up.
MAIN OUTCOMES AND MEASURES
The primary outcome was the change in the NRS-11 scores from baseline to week 4, with responders defined as participants achieving a 30% or more reduction in NRS-11 scores.
RESULTS
Of 448 participants, the mean (SD) age was 63.19 (9.26) years, 233 (52.01%) were male, and 215 were female (47.99%). At week 4, the electroacupuncture group had a greater decrease in the NRS-11 scores (−1.52) than the sham electroacupuncture group (−0.99) with an adjusted mean difference of −0.53 (95% CI, −0.61 to −0.43; P < .001), and the responder rate was significantly higher in the electroacupuncture group (46.68%) than in the sham electroacupuncture group (24.28%) (adjusted risk difference, 22.40%; 95% CI, 13.02%-31.79%; P < .001). These treatment benefits persisted through a 1-month follow-up; no clinically significant adverse events were observed.
CONCLUSIONS AND RELEVANCE
Among patients with PHN in this study, electroacupuncture provided a statistically significant reduction in pain severity, increased responder rates, and improved pain-related functional outcomes. These benefits suggest that electroacupuncture may be a useful nonpharmacological option for integrated management of PHN.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04560361.
Introduction
Postherpetic neuralgia (PHN) is characterized by debilitating pain within the dermatomal region persisting for at least 90 days following the onset of the herpes zoster rash. The incidence of PHN among patients with herpes zoster ranges from 5% to 32%, with risk increasing with age. Population-based studies in the US report an overall PHN incidence of 5.75 per 10 000 person-years. In China, with an annual herpes zoster incidence of 58.5 per 10 000 person-years, approximately 15.84% of patients develop PHN. This condition substantially impairs quality of life, causing sleep disturbances, somatosensory abnormalities, and psychological distress, and imposes significant economic burden. Clinical management includes topical agents (lidocaine or capsaicin) and systemic therapies, including anticonvulsants (gabapentin or pregabalin), tricyclic antidepressants, or opioid analgesics.
Acupuncture, a core component of traditional Chinese medicine, is widely used for chronic neuropathic pain management, with PHN being a common indication. Electroacupuncture, which integrates traditional needle insertion with electrical stimulation, can enhance analgesic effects through neural activity modulation. Electroacupuncture has been investigated across various neuropathic pain conditions. Studies suggest that electroacupuncture reduces pain intensity in chemotherapy-induced peripheral neuropathy, improves pain scores and quality of life in painful diabetic peripheral neuropathy, and provides pain relief with a favorable safety profile in trigeminal neuralgia. In a Chinese expert consensus, electroacupuncture is considered a potential adjunctive therapy for PHN. Although some systematic reviews have indicated benefits of acupuncture for PHN, few have specifically evaluated electroacupuncture, and high-quality evidence remains limited. Moreover, existing randomized clinical trials (RCTs) investigating acupuncture or electroacupuncture for PHN are often limited by small sample sizes, absence of sham controls, and single-center designs, which limit the reliability and generalizability of their findings. Therefore, we conducted a multicenter, randomized, sham-controlled clinical trial to rigorously evaluate the efficacy and safety of electroacupuncture in patients with PHN.
Methods
Design, Organization, and Oversight
This multicenter, randomized, sham-controlled clinical trial was conducted at 7 tertiary hospitals in China between October 14, 2020, and September 28, 2022 (NCT04560361). The study protocol was approved by the institutional review boards of the coordinating center and each study site (Supplement 1). Written informed consent was obtained from all participants before randomization. The trial duration was approximately 10 weeks and included a washout period of 7 days or longer (detailed in Supplement 1), 3- to 7-day screening observation period, 4-week treatment period, and 1-month follow-up period. No patients or public were involved in the study design, recruitment, conduct, or interpretation, as the research predated formal patient involvement procedures in China. The trial was conducted according to the Declaration of Helsinki. This study adhered to the Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines.
Trial Population
The study population included adults aged 45 to 75 years who met the diagnostic criteria for PHN according to the European consensus-based guideline and demonstrated moderate to severe pain, defined as a mean 11-point Numeric Rating Scale (NRS-11) score 4 or more during screening (Figure 1). Key exclusion criteria included concurrent use of multiple permitted PHN medications or use of prohibited treatments within 14 days before screening and refusal to complete washout, serious safety problems that occurred during the washout or observation periods, uncontrolled severe comorbidities, non-PHN–related pain conditions, and a history of nerve interventions or neurosurgical treatments for PHN (eg, nerve ablation) (details in Supplement 1). All participants were recruited from China and were of Asian descent. Patients self-reported the following ethnicities: Han, Hui, or Manchu (verified by their identification cards).
Figure 1. Flow of Participants in the Trial.
NRS-11 indicates 11-point Numeric Rating Scale; PHN, postherpetic neuralgia.
Trial Procedures
Eligible participants were randomly assigned in a 1:1 ratio to receive either electroacupuncture or sham electroacupuncture treatment. Randomization was stratified by enrollment site using dynamic block randomization (with block sizes of 4, 6, and 8), with allocation concealment maintained throughout the trial. An independent statistician generated and validated the randomization sequence, which was subsequently uploaded to the Electronic Data Capture System of the Affiliated Hospital of Nanjing University of Chinese Medicine. The sequence was securely managed by a trial administrator uninvolved in the study. Participants, outcome assessors, and statisticians were blinded to group allocation; acupuncturists were not.
Patients were permitted to continue stable concomitant medications for underlying conditions. For PHN, only 1 stable concomitant analgesic (eg, pregabalin, gabapentin, or carbamazepine) stable for 14 days or more before screening was permitted and maintained unchanged unless safety issues arose. All other PHN-related treatments, including topical agents, muscle relaxants, antipsychotics, and unapproved analgesics, were prohibited (Supplement 1). Paracetamol tablets (≤2.0 g per day) were provided as a rescue analgesic, and all use was recorded.
Electroacupuncture and sham electroacupuncture were administered by 7 centrally trained licensed acupuncturists using Hwato disposable needles (0.30 × 40 mm), placebo blunt needles (0.30 × 25 mm), insulating adhesive pads, and SDZ-V electroacpuncture apparatuses (Suzhou Medical Instrument). Detailed acupoint localization, needling techniques, and equipment setup are shown in Figure 2 and eTable 1 in Supplement 2.
Figure 2. Illustration of Electroacupuncture and Sham Electroacupuncture Procedures for Postherpetic Neuralgia.
A, Location of acupoints used in the study. On the ipsilateral (postherpetic neuralgia–affected side), needles were inserted at Zhigou (SJ6), Yanglingquan (GB34), and Ashi points (2-3 cm intervals around the painful area). B, Comparison of needling techniques between electroacupuncture and sham electroacupuncture groups. Needles were inserted vertically at SJ6/GB34 (15-20 mm) and obliquely at Ashi points (30°-45°; 10 mm). The electroacupuncture group used penetrating Hwato disposable acupuncture needles (0.30 × 40 mm), while the sham electroacupuncture group used placebo blunt needles (0.30 × 25 mm) placed through adhesive pads until contacting the insulating adhesive layer, ensuring no skin penetration. C, Equipment and connection setup. Electrical stimulation (2 Hz continuous wave, 1-5 mA) was applied for 30 minutes via electrodes connected to needle handles at SJ6/GB34 and to the proximal-distal pairs of Ashi needles along the painful region. In the sham electroacupuncture group, electrodes were placed identically, but current was blocked by the insulating adhesive layer. D, Timeline of the study.
For the electroacupuncture group, ipsilateral Zhigou (SJ6), Yanglingquan (GB34), and Ashi points (2-3 cm intervals around the painful area) were punctured to elicit de-qi (soreness, numbness, distention, or heaviness). Needle insertion was vertical for SJ6/GB34 (15-20 mm) and oblique for Ashi points (30°-45°; 10 mm). Electrical stimulation (2-Hz continuous wave; 1-5 mA) was then applied for 30 minutes, adjusted to induce mild periacupoint muscle twitching.
In the sham electroacupuncture group, placebo blunt needles were placed on the same acupoints without skin penetration or needle manipulation. Electrodes were attached identically, but no effective electrical stimulation was delivered because the current was blocked by an insulating adhesive layer. Both groups received 20 sessions over 4 weeks (once daily, 5 times weekly).
Outcomes
The primary outcome was the patient-reported change from baseline in the NRS-11 pain scores at week 4. Participants with a reduction of 30% or more in the NRS-11 scores were considered responders. A reduction of 1.5 points was defined as the minimal important difference (MID) based on published literature and was used as a post hoc interpretive benchmark for the primary outcome. This threshold was derived from an anchor-based method for pain intensity on a 0 to 10 scale, as established in a methodological framework for MID selection and subsequently applied in a large systematic review of interventional procedures for chronic pain.
Secondary outcomes included visual analog scale (VAS), Verbal Rating Scale (VRS), mechanical pain threshold, pain area, mean number of pain episodes, and mean duration of each pain episode. We used additional standardized questionnaires to assess specific domains: pain characteristics were assessed using the Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2), pain severity and pain-related interference with daily activities using the Zoster Brief Pain Inventory (ZBPI), emotional and psychological functioning using the Depression, Anxiety and Positive Outlook Scale (DAPOS), and overall treatment response using the Patient Global Impression of Change (PGIC). All outcomes were assessed at multiple time points (detailed in Supplement 1).
Safety was monitored throughout the study, with adverse events and serious adverse events recorded. Exploratory analyses included rescue analgesic use and the reduction or discontinuation of concomitant pain medications.
Statistical Analysis
Sample Size
Based on previous studies and our pilot study, we anticipated a between-group difference of 1.20 (SD, 3.50) favoring electroacupuncture over sham electroacupuncture. To achieve 90% power at a 2-sided significance level of .05, a sample size of 374 was required. Allowing for a 20% dropout rate, we planned to recruit 448 participants (224 per group).
The anticipated difference of 1.20 points was used for power calculation and differs from the post hoc MID threshold of 1.5 points, which was defined based on published literature to aid clinical interpretation. The distinction between the powering assumption and the MID benchmark reflects the difference between statistical planning and clinical interpretability.
Efficacy Outcomes
An interim analysis was triggered after 50% of the planned sample size had completed the primary outcome visit, with blinded data review followed by unmasking and review by the data and safety monitoring panel. The O’Brien-Fleming α-spending function was used to control the overall type I error rate (α = .474), yielding an adjusted 2-sided significance boundary of P < .008 (information fraction: 273 of 448; 0.61) for efficacy at the interim stage. At the interim analysis, the between-group difference in the primary outcome (mean change in NRS-11 score) was −0.36 (95% CI, −0.59 to −0.13; P = .002) and crossed the prespecified statistical stopping boundary (eTables 2 and 3 in Supplement 2). However, the monitoring panel recommended trial continuation owing to no safety concerns and the observed effect size being substantially below the MID (eTable 4 in Supplement 2). The final analysis was therefore conducted with the corresponding adjusted significance level of P < .047. For all secondary and exploratory outcomes, a 2-sided P < .05 denoted statistical significance.
The primary analysis was conducted in the intention-to-treat population. Missing primary outcome data were imputed under the missing-at-random assumption. One hundred datasets were generated using a fully conditional specification. Each imputed dataset was analyzed using mixed model for repeated measures (MMRM), with the Kenward-Roger method applied to estimate degrees of freedom. Results were pooled using the Rubin rules. The primary outcome analysis used a random-intercept MMRM adjusted for enrollment site. The model included baseline value as a fixed-effect covariate and fixed-effect categorical factors for treatment group, visit, and the treatment-by-visit interaction. Between-group differences at each visit were estimated as least-squares mean differences with corresponding 95% CIs and P values. Responder rates were analyzed separately using a repeated measures generalized linear model with a binomial distribution and identity link, incorporating the same covariate as the MMRM.
The same MMRM approach was applied to continuous longitudinal secondary outcomes (VAS, mechanical pain threshold, pain area, SF-MPQ-2, ZBPI, and DAPOS). For ordinal outcomes (VRS, mean number of pain episodes, mean duration of each pain episode, and PGIC), the Wilcoxon rank sum test was used for between-group comparisons. For secondary outcomes, missing data were not imputed, and analyses were based on observed data. Adverse events were summarized descriptively.
Prespecified secondary outcomes included VAS, VRS, mechanical pain threshold, pain area, mean number of pain episodes, mean duration of each pain episode, SF-MPQ-2, ZBPI, DAPOS, PGIC, and safety outcomes. Post hoc analyses included rescue analgesic use and reduction or discontinuation of concomitant pain medications, post hoc sensitivity analyses (per-protocol, last observation carried forward imputation, additional covariate adjustment, and exclusion of participants with local subcutaneous bruising in the electroacupuncture group), and post hoc subgroup analyses (by sex, baseline NRS-11, PHN duration, and concomitant medication use).
All analyses were performed by an independent statistician using SAS version 9.4 (SAS Institute).
Results
Study Population
Between October 14, 2020, and August 23, 2022, 1072 participants were screened, of whom 448 were randomly assigned to the electroacupuncture or sham electroacupuncture groups; 383 (85.49%) completed the trial (Figure 1). Baseline characteristics were comparable between groups, including PHN location distribution, with the only exception being the ZBPI pain severity score (Table 1). The mean (SD) age of the participants was 63.19 (9.26) years, 233 (52.01%) were male, and 215 were female (47.99%). The mean (SD) PHN duration was 1.57 (2.55) years and the mean (SD) baseline pain intensity, measured by NRS-11, was 5.75 (1.13). Permitted concomitant PHN medications were used by 46 participants (20.44%) in the electroacupuncture group and 56 (25.11%) in the sham electroacupuncture group; nevertheless, all reported moderate to severe pain and were included in the analysis.
Table 1. Baseline Characteristics of Participants.
| Characteristics | No. (%) | ||
|---|---|---|---|
| Electroacupuncture (n = 225) | Sham electroacupuncture (n = 223) | Total (n = 448) | |
| Age | |||
| Mean (SD), y | 63.60 (9.05) | 62.78 (9.47) | 63.19 (9.26) |
| Sexa | |||
| Male | 117 (52.00) | 116 (52.02) | 233 (52.01) |
| Female | 108 (48.00) | 107 (47.98) | 215 (47.99) |
| Ethnicitya | |||
| Han | 223 (99.11) | 223 (100) | 446 (99.55) |
| Hui | 1 (0.44) | 0 | 1 (0.22) |
| Manchu | 1 (0.44) | 0 | 1 (0.22) |
| BMI, mean (SD)b | 23.35 (2.53) | 23.31 (2.37) | 23.33 (2.45) |
| Education level | |||
| Primary education or less | 46 (20.44) | 49 (21.97) | 95 (21.21) |
| Secondary education | 127 (56.44) | 128 (57.40) | 255 (56.92) |
| Tertiary education | 52 (23.11) | 46 (20.63) | 98 (21.88) |
| Concomitant pain medications for PHN | 46 (20.44) | 56 (25.11) | 102 (22.77) |
| Pregabalin | 28 (12.44) | 28 (12.56) | 56 (12.50) |
| Gabapentin | 17 (7.56) | 25 (11.21) | 42 (9.38) |
| Chinese patent medicine | 1 (0.44) | 0 | 1 (0.22) |
| Carbamazepine | 0 | 2 (0.90) | 2 (0.45) |
| Other | 0 | 1 (0.45) | 1 (0.22) |
| PHN duration, mean (SD), y | 1.56 (2.43) | 1.57 (2.68) | 1.57 (2.55) |
| Area of the pain site in PHN, mean (SD), ×100 m2c | 2.99 (1.97) | 3.09 (2.50) | 3.04 (2.25) |
| Location of PHN | |||
| Trigeminal region | 40 (17.94) | 41 (18.22) | 81 (18.08) |
| Cervical region | 15 (6.72) | 16 (7.11) | 31 (6.92) |
| Thoracic region | 92 (41.26) | 96 (42.67) | 188 (41.96) |
| Lumbosacral and abdominal region | 46 (20.63) | 45 (20.00) | 91 (20.31) |
| Extremities | 27 (12.11) | 24 (10.67) | 51 (11.38) |
| Other | 3 (1.35) | 3 (1.33) | 6 (1.34) |
| Mechanical pain threshold, mean (SD)d | 3.91 (21.48) | 3.12 (9.82) | 3.52 (16.71) |
| NRS-11 score, mean (SD)e,f | 5.67 (1.11) | 5.83 (1.16) | 5.75 (1.13) |
| VAS score, mean (SD)e,g | 59.08 (11.47) | 60.84 (11.39) | 59.96 (11.45) |
| VRS score, mean (SD)e,h | |||
| Mild | 91 (40.81) | 77 (34.68) | 168 (37.75) |
| Moderate | 122 (54.71) | 138 (62.16) | 260 (58.43) |
| Severe | 10 (4.48) | 7 (3.15) | 17 (3.82) |
| SF-MPQ-2 score, mean (SD)i | |||
| Continuous pain | 5.20 (5.83) | 5.28 (5.96) | 5.24 (5.89) |
| Intermittent pain | 6.40 (6.31) | 7.48 (7.36) | 6.94 (6.87) |
| Neuropathic pain | 7.63 (5.84) | 7.78 (6.56) | 7.70 (6.20) |
| Affective descriptors | 4.85 (5.52) | 5.02 (5.32) | 4.85 (5.41) |
| ZBPI score, mean (SD)j | |||
| Pain severity score | 5.20 (1.13) | 5.45 (1.13) | 5.33 (1.14) |
| Pain interference score | 3.61 (1.49) | 3.77 (1.53) | 3.69 (1.51) |
| DAPOS score, mean (SD)e,k | |||
| Depression | 9.87 (3.81) | 9.98 (4.14) | 9.93 (3.97) |
| Anxiety | 5.88 (2.59) | 5.67 (2.73) | 5.78 (2.66) |
| Positive outlook | 7.87 (1.91) | 7.75 (2.00) | 7.81 (1.95) |
Abbreviations: BMI, body mass index; DAPOS, Depression, Anxiety and Positive Outlook Scale; NRS-11, 11-point Numeric Rating Scale; PGIC, Patient Global Impression of Change; PHN, postherpetic neuralgia; SF-MPQ-2, Short-form McGill Pain Questionnaire 2; VAS, visual analog scale; VRS, Verbal Rating Scale; ZBPI, Zoster Brief Pain Inventory.
Sex and ethnicity reported by the patient and verified by identification card.
Calculated as weight in kilograms divided by height in meters squared.
The pain area was calculated based on a 45-zone body surface area method: body surface area (m2) × percentage of the pain area code × percentage of the PHN area on the pain area.
Mechanical pain threshold, determined as the geometric mean of 5 measurements with a Von Frey filament (electroacupuncture group, n = 215; sham electroacupuncture group, n = 213).
Data available for electroacupuncture group (n = 223) and sham electroacupuncture group (n = 222).
NRS-11: 0 (no pain) to 10 (worst pain imaginable).
VAS: 0 (no pain) to 100 (worst pain imaginable).
VRS categories: 0 (painless), 1 (mild), 2 (moderate), or 3 (severe).
SF-MPQ-2 measures continuous, intermittent, neuropathic, and affective pain qualities.
ZBPI assesses pain severity and related interference in daily life.
DAPOS measures depressive symptoms, anxiety, and positive outlook.
Primary and Prespecified Secondary Outcomes
At week 4, the electroacupuncture group exhibited greater reduction in the NRS-11 scores (mean change, −1.52; 95% CI, −1.58 to −1.46) than the sham electroacupuncture group (−0.99; 95% CI, −1.04 to −0.93), with an adjusted mean difference of −0.53 (95% CI, −0.61 to −0.43; P < .001), which is below the MID. The responder rates were significantly higher in the electroacupuncture group than in the sham electroacupuncture group, with adjusted risk differences of 22.40% (95% CI, 13.02%-31.79%; P < .001) at week 4 (Figure 3; eTable 5 in Supplement 2).
Figure 3. Graphs and Plots of Primary and Secondary Outcomes.
A, Mean change from baseline in the 11-point Numeric Rating Scale (NRS-11) pain scores over time. B, Responder rate, proportion of patients achieving 30%, or more reduction in NRS-11 scores from baseline over time. C, Forest plot showing adjusted risk differences with 95% CIs for responder rates, rescue analgesic use, and reduction or discontinuation of concomitant analgesics. The adjusted risk difference for rescue analgesic use has been inverted (multiplied by −1) so that for all outcomes, positive values favor electroacupuncture. PHN indicates postherpetic neuralgia.
The treatment benefits of electroacupuncture persisted at week 8, with a between-group difference in change from baseline in NRS-11 scores of −0.60 (95% CI, −0.71 to −0.49; P < .001) and a responder rate difference of 21.65% (95% CI, 12.79%-30.52%; P < .001) at week 8 (Figure 3; eTable 5 in Supplement 2).
VAS scores confirmed significantly greater pain reduction in the electroacupuncture group (eTable 5 in Supplement 2). VRS categories differed significantly between groups starting from week 2 through week 8. At week 4, more electroacupuncture participants reported mild pain and fewer reported moderate or severe pain (eTable 6 in Supplement 2). No significant between-group differences were observed in mechanical pain threshold, pain area, mean number of pain episodes, or mean duration of each pain episode (eTables 5, 7, and 8 in Supplement 2).
SF-MPQ-2 subscales confirmed greater improvements in multiple pain domains with electroacupuncture (eTable 5 in Supplement 2). These benefits were reflected in ZBPI pain interference scores (eTable 5 in Supplement 2). Item-level analyses revealed greater improvements in mood and sleep at both time points. Significant benefits were also observed for general activity and enjoyment of life at week 8 (eTable 9 in Supplement 2). DAPOS questionnaire results suggested that electroacupuncture led to significantly greater reductions in anxiety at week 4 and in both depression and anxiety at week 8 compared with sham electroacupuncture, with no significant difference in positive outlook subscale (eTable 5 in Supplement 2). For PGIC, patients in the electroacupuncture group reported greater global improvement at both week 4 and week 8 compared with the sham electroacupuncture group (eFigures 1 and 2 in Supplement 2).
Adverse Events
Treatment-related adverse events included 14 cases in the electroacupuncture group (13 local subcutaneous bruising at the needling site and 1 sharp pain) and 3 cases in the sham electroacupuncture group (all sharp pain). All treatment-related events were mild (grade 1, according to Common Terminology Criteria for Adverse Events version 5.0), requiring no intervention. Adverse events unrelated to treatment were all COVID-19 cases (electroacupuncture group, 3; sham electroacupuncture group, 5). No serious adverse events were reported (Table 2).
Table 2. Adverse Events Related and Unrelated to Treatment.
| AE | Electroacupuncture (n = 225) | Sham electroacupuncture (n = 223) | ||
|---|---|---|---|---|
| Participants, No. (%)a | Events, No. | Participants, No. (%)a | Events, No. | |
| Overall | 17 (7.56) | 17 | 8 (3.59) | 8 |
| SAEsb | 0 | 0 | 0 | 0 |
| Related to the treatment | ||||
| Local subcutaneous bruising at the needling site | 13 (5.78) | 13 | 0 | 0 |
| Sharp pain | 1 (0.44) | 1 | 3 (1.35) | 3 |
| Unrelated to treatment | ||||
| COVID-19 | 3 (1.33) | 3 | 5 (2.24) | 5 |
Abbreviations: AE, adverse event; SAE, serious adverse event.
AEs were counted by the type rather than the frequency for the same participant. AEs of different types occurring in 1 participant were defined as separate AEs; an AE that occurred multiple times in 1 participant was defined as 1 AE.
An SAE was defined as an AE that caused hospitalization, surgery, exacerbation of the preexisting condition, or death.
Post Hoc Analyses
EA was also associated with lower rescue analgesic use (6.67% vs 13.90%; adjusted risk difference, −7.23%; 95% CI, −12.82% to −1.65%; P = .01) and a higher proportion of concomitant pain medication reduction or discontinuation (23.91% vs 8.93%, adjusted risk difference, 14.98%; 95% CI, 0.57%-29.40%; P = .04) (Figure 3).
Sensitivity analyses using per-protocol population, last observation carried forward imputation, additional adjustment for baseline ZBPI pain severity score, and exclusion of participants with local subcutaneous bruising in the electroacupuncture group yielded consistent findings with the primary analysis (eTables 10-13 in Supplement 2). Subgroup analyses suggested that the treatment effect was consistent across most subgroups, except among participants receiving concomitant PHN medications, where the between-group difference did not reach statistical significance (eTable 14 in Supplement 2).
Discussion
In this multicenter trial of electroacupuncture involving patients with PHN, 4 weeks of electroacupuncture treatment produced greater reductions in NRS-11 scores compared with sham electroacupuncture, although the difference did not reach the MID. The effects persisted for at least 4 weeks posttreatment and the occurrence of adverse events was relatively low.
This largest multicenter RCT of electroacupuncture for PHN yielded findings consistent with prior evidence from acupuncture-related research. A meta-analysis of acupuncture-related therapies reported significant pain reduction in PHN (pooled standardized mean difference [SMD], −1.78), with a subgroup analysis of electroacupuncture showing a similarly favorable effect (SMD, −1.28). The responder rate difference suggests that electroacupuncture increases the likelihood of achieving 30% or more pain reduction, complementing the modest average treatment effect observed in the primary outcome.
Although prior research supports electroacupuncture’s efficacy for PHN, most studies have compared electroacupuncture combined with medications vs medications alone, limiting independent effect assessment. Additionally, a network meta-analysis could not include sham electroacupuncture controls because of insufficient eligible studies. Therefore, our trial directly compared electroacupuncture with a sham electroacupuncture procedure using nonpenetrating needles at real acupoints, with electrodes attached but electrical current blocked by an insulating layer, designed to be credible while minimizing physiological activity. The results showed that both electroacupuncture and sham electroacupuncture induced pain reductions in patients with PHN. The reduction observed in the sham electroacupuncture group (approximately 1 point on the NRS-11) aligns with the known placebo effect reported in previous PHN trials (1.16 points; 95% CI, 1.03-1.29), and the modest between-group difference observed here is consistent with individual patient-data meta-analyses across chronic pain conditions. The higher dropout rate in the sham electroacupuncture group (18.39% vs 8.89%) suggests that its nonspecific benefits were not consistently substantial. This differential attrition may overestimate sham electroacupuncture’s effect in completer analyses, as those who discontinued were likely nonresponders.
A key clinical observation from this study was that a significant between-group difference in NRS-11 scores emerged at week 2, after 10 treatment sessions, indicating a cumulative analgesic effect of electroacupuncture in PHN, consistent with prior evidence. The delayed emergence of this intergroup difference suggests that achieving optimal efficacy likely requires a sufficient number of treatment sessions administered over an adequate duration. This delayed onset underscores the clinical importance of completing a treatment course to fully realize the potential benefits of electroacupuncture.
Our findings also reveal that electroacupuncture significantly reduced patient-reported pain intensity but did not alter objective clinical indicators of peripheral pathophysiology, such as pain area or threshold. Thus, the primary electroacupuncture mechanism is likely mediated through activating endogenous neuromodulatory systems and descending inhibitory pathways attenuating pain perception in PHN. Future studies using functional neuroimaging could directly test this hypothesis by correlating electroacupuncture-induced analgesia with changes in connectivity within descending pain modulatory networks.
Furthermore, this study highlights notable clinical advantages of electroacupuncture over sham electroacupuncture in pain management. Fewer participants in the electroacupuncture group required rescue analgesics (6.67% vs 13.90%), reflecting a more stable and sustained analgesic effect. Additionally, a higher proportion of participants in the electroacupuncture group reduced or discontinued concomitant pain medications (23.91% vs 8.93%), underscoring electroacupuncture’s potential to decrease reliance on routine analgesics, which may in turn reduce the risk of drug-related adverse reactions and improve long-term treatment compliance.
Electroacupuncture also improved emotional well-being. Chronic pain is frequently accompanied by clinically significant anxiety and depression, contributing to disproportionate functional impairment. Using the validated DAPOS scale, we observed that electroacupuncture reduced anxiety at week 4 and week 8 and improved depression at week 8 compared with sham electroacupuncture, indicating benefits beyond analgesia. Thus, electroacupuncture may address the affective dimension of PHN, often undertreated in clinical practice.
Limitations
This study has limitations. First, although the 1-month follow-up period demonstrated persistence of the electroacupuncture effect, long-term maintenance was not evaluated. Second, although the sham electroacupuncture group received nonpenetrating blunt needles without electrical stimulation, these procedures may have produced physiological or nonspecific placebo effects, potentially biasing effect estimates. Third, we did not formally assess prior acupuncture experience, blinding success, or treatment expectations, limiting our ability to exclude expectation effects and assessment bias. The higher rate of local subcutaneous bruising in the electroacupuncture group (5.78% vs 0%) may have led to unblinding in a small subset of participants. However, blinding was successfully maintained in our prior study using the same device and a post hoc sensitivity analysis excluding the 13 participants with bruising in the electroacupuncture group yielded results consistent with the primary analysis. While bruising may not fully capture all potential unblinding, this analysis suggests that the treatment effect was not disproportionately driven by this small subgroup. Fourth, generalizability is limited by the specific age range (45 to 75 years) and exclusively Chinese population; external validation in broader populations is warranted. Lastly, the study relied primarily on patient-reported pain scores; future research could incorporate more objective physiological indicators, such as quantitative sensory testing or neurophysiological assessments.
Conclusions
Although the mean reduction in pain intensity with electroacupuncture did not reach the post hoc MID compared with sham electroacupuncture, a 4-week course of electroacupuncture significantly improved responder rates and alleviated pain-related emotional distress in patients with PHN. These benefits persisted for at least 1 month posttreatment, supporting electroacupuncture as a viable nonpharmacological approach for integrated symptom management. Further research should investigate its long-term efficacy and underlying neural mechanisms.
Trial protocol
eTable 1. Location of Acupoints for EA and SA Groups
eTable 2. Baseline Characteristics of Participants from the Interim Analysis
eTable 3. Quantitative Outcomes at Time Points from the Interim Analysis
eTable 4. Adverse Events Related to Treatment from the Interim Analysis
eTable 5. Primary Outcome and Secondary Outcomes
eTable 6. Verbal Rating Scale at Each Visit Time
eTable 7. Average Number of Pain Episodes at Each Visit Time
eTable 8. Average Duration of Each Pain Episode at Each Visit Time
eTable 9. Change from Baseline in ZBPI Pain Severity Item and Interference Item Scores
eTable 10. Sensitivity Analyses for the Primary Outcome based on Per-protocol Population
eTable 11. Sensitivity Analysis for the Primary Outcome by Imputation of Missing Data by the Last Observation Carried Forward Method
eTable 12. Sensitivity Analysis for the Primary Outcome by Adding the Baseline ZBPI Pain Severity Score Adjusted
eTable 13. Sensitivity Analysis for the Primary Outcome by excluding participants with local subcutaneous bruising in the EA group
eTable 14. Subgroup Analyses for the Primary Outcome
eFigure 1. Patient Global Impression of Change at Week 4
eFigure 2. Patient Global Impression of Change at Week 8
Data sharing statement
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Trial protocol
eTable 1. Location of Acupoints for EA and SA Groups
eTable 2. Baseline Characteristics of Participants from the Interim Analysis
eTable 3. Quantitative Outcomes at Time Points from the Interim Analysis
eTable 4. Adverse Events Related to Treatment from the Interim Analysis
eTable 5. Primary Outcome and Secondary Outcomes
eTable 6. Verbal Rating Scale at Each Visit Time
eTable 7. Average Number of Pain Episodes at Each Visit Time
eTable 8. Average Duration of Each Pain Episode at Each Visit Time
eTable 9. Change from Baseline in ZBPI Pain Severity Item and Interference Item Scores
eTable 10. Sensitivity Analyses for the Primary Outcome based on Per-protocol Population
eTable 11. Sensitivity Analysis for the Primary Outcome by Imputation of Missing Data by the Last Observation Carried Forward Method
eTable 12. Sensitivity Analysis for the Primary Outcome by Adding the Baseline ZBPI Pain Severity Score Adjusted
eTable 13. Sensitivity Analysis for the Primary Outcome by excluding participants with local subcutaneous bruising in the EA group
eTable 14. Subgroup Analyses for the Primary Outcome
eFigure 1. Patient Global Impression of Change at Week 4
eFigure 2. Patient Global Impression of Change at Week 8
Data sharing statement
