The Efficacy of High-frequency Short-time Spinal Cord Stimulation in the Treatment of Herpes Zoster-associated Neuralgia

April 25, 2025 updated by: Li Zhao

Zoster-associated neuralgia (ZAN) is a type of neuropathic pain caused by the reactivation of the varicella-zoster virus (VZV). The global annual incidence is approximately 3-5 per 1,000 individuals, and in China, the incidence is around 4.89 per 1,000 individuals, increasing with age. The underlying mechanisms of ZAN involve neuroinflammation, peripheral and central sensitization, and other factors, ultimately leading to anxiety, depression, and significant reductions in quality of life. Treating ZAN remains challenging.

Spinal cord stimulation (SCS) alleviates pain via multiple mechanisms, including the gate control theory, modulation of neurotransmitters (e.g., gamma-aminobutyric acid), suppression of neuroinflammation (e.g., reduced levels of IL-1β and TNF-α), and promotion of autophagy. However, traditional low-frequency SCS (30-100 Hz) is limited by incomplete pain coverage, reduced long-term efficacy, and side effects such as paresthesia (e.g., tingling sensations).

High-frequency SCS (HF-SCS, 1,000 Hz) offers pain relief without inducing paresthesia. Studies have suggested that it may be superior to traditional SCS. However, clinical data on the use of HF-SCS in ZAN are limited, and no such studies have been conducted in China.

This study aims to compare the efficacy of short-term high-frequency (1 kHz) SCS with traditional low-frequency SCS in the treatment of ZAN. By evaluating outcomes such as pain relief (NRS scores), improvements in anxiety and depression (HADS), sleep quality (PSQI), patient-reported experience, and complication rates, this research seeks to assess the safety and efficacy of short-term HF-SCS, thereby potentially providing a novel therapeutic strategy for patients with ZAN.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Zoster-associated neuralgia (ZAN) refers to neuropathic pain resulting from herpes zoster (HZ) infection. Based on the duration of symptoms, ZAN is classified into three stages: acute herpetic neuralgia (AHN, less than 1 month), subacute herpetic neuralgia (SHN, 1 to 3 months), and postherpetic neuralgia (PHN, more than 3 months).The global annual incidence of HZ is approximately 3 to 5 per 1,000 individuals, with higher rates observed among individuals aged 50 years and older, and among females. In China, the annual incidence is approximately 4.89 per 1,000 individuals, with a notable increase observed with advancing age.

Pain is the most common clinical symptom of HZ, and its severity correlates with age, immune status, and initial pain intensity. Older adults and immunocompromised patients are more prone to developing PHN . HZ may also lead to complications such as ocular herpes zoster, meningitis, and motor nerve damage, particularly in immunocompromised individuals, where the risk and severity of these complications are significantly elevated . The pathogenesis of PHN remains incompletely understood and may involve inflammatory responses, ion channel alterations, and peripheral/central sensitization . Chronic pain severely impacts patients' quality of life and can lead to psychological issues such as anxiety, depression, and sleep disturbances, imposing substantial burdens on families and society .

ZAN is challenging to treat, with current approaches including pharmacotherapy, nerve blocks, pulsed radiofrequency, and spinal cord stimulation (SCS) . SCS is a minimally invasive neuromodulation technique widely used for chronic pain. It involves implanting electrodes in the epidural space to deliver electrical pulses to the dorsal columns and dorsal horn structures, thereby modulating pain signal transmission. Although the analgesic mechanism of SCS is not fully elucidated, its theoretical basis dates back to the 1965 "gate control theory" proposed by Melzack and Wall. This theory posits that activating large-diameter Aβ afferent fibers inhibits nociceptive signals mediated by small-diameter Aδ and C fibers, reducing spinal sensitization .

Recent studies suggest that SCS also regulates neurotransmitters, suppresses neuroinflammation, and modulates autophagy . At the neurotransmitter level, SCS enhances the release of γ-aminobutyric acid (GABA), reduces glutamate concentrations, amplifies endogenous opioid signaling, and activates the endocannabinoid system, thereby rebalancing dorsal horn activity and inhibiting pain transmission. In neuroinflammatory regulation, SCS elevates anti-inflammatory resolvin D1, reduces pro-inflammatory cytokines (IL-1β, TNF-α), suppresses microglial overactivation, and modulates the p38MAPK pathway, thereby attenuating neuroinflammation and pain hypersensitivity . Additionally, SCS promotes neuronal autophagy, accelerating the clearance of damaged cellular components to restore function and mitigate neural injury, further alleviating pain . These mechanisms collectively support SCS as a multimodal analgesic strategy, driving its clinical adoption.

SCS has shown efficacy in ZAN treatment, particularly for patients refractory to medications or other minimally invasive therapies. However, traditional low-frequency SCS (30-100 Hz), which relies on high-intensity pulses to modulate spinal and ascending pain pathways, often induces paresthesia (e.g., tingling) as a side effect. Clinical limitations include incomplete pain coverage, diminishing efficacy over time, and discomfort in non-target areas, necessitating novel SCS paradigms with improved efficacy and tolerability .

High-frequency spinal cord stimulation (HF-SCS) is an emerging neuromodulation technique that alleviates chronic neuropathic pain without paresthesia and may benefit patients unresponsive to traditional SCS. In China, HF-SCS research remains exploratory, with no clinical studies on ZAN. International studies, though advanced, lack systematic data on ZAN, with heterogeneous parameters (indications, frequency, pulse width, etc.). This study compares short-term 1 kHz HF-SCS with traditional low-frequency SCS in ZAN treatment, evaluating pain relief, psychological status (anxiety/depression), sleep quality, patient experience, and complication rates. The findings aim to establish the safety and efficacy of short-term HF-SCS for ZAN, offering a novel therapeutic option for this challenging condition.

Study Type

Observational

Enrollment (Estimated)

74

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guizhou
      • Zunyi, Guizhou, China, 563000
        • Recruiting
        • 149 Dalian Road, Huichuan District, Zunyi City, Guizhou Province
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients diagnosed with herpes zoster-associated neuralgia undergoing spinal cord electrical stimulation (SCS) surgery.

Description

Inclusion Criteria:

  1. Patients with inadequate response to non-surgical treatments such as pharmacotherapy;
  2. Patients with major organ dysfunction intolerant to drug therapy;
  3. Patients with systemic comorbidities (e.g., hypertension, diabetes mellitus);
  4. Patients with moderate to severe pain intensity (Numerical Rating Scale [NRS] score ≥ 4).

Exclusion Criteria:

  1. Patients with severe psychiatric disorders;
  2. Patients with severe local or systemic infections at the puncture site;
  3. Patients with severe coagulopathies (platelet count < 80×10⁹/L during puncture) or those requiring uninterrupted anticoagulation therapy without bridging protocol;
  4. Patients with end-stage organ failure who cannot maintain prone positioning or tolerate the procedure;
  5. Patients with severe spinal stenosis, vertebral ankylosis, or scoliosis;
  6. Patients with language barrier or impaired communication abilities.ion

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
HF group
HF-SCS parameter settings: Frequency 1000 Hz, pulse width 60-180 μs, amplitude 0.5-3.0 V
Other: HF-SCS parameter settings: Frequency 1000 Hz, pulse width 60-180 μs, amplitude 0.5-3.0 V
HF-SCS parameter settings: Frequency 1000 Hz, pulse width 60-180 μs, amplitude 0.5-3.0 V
LF group
LH-SCS parameter settings: Frequency 30-100 Hz, pulse width 100-300 μs, amplitude 0.5-5.0 V
Other: LH-SCS parameter settings: Frequency 30-100 Hz, pulse width 100-300 μs, amplitude 0.5-5.0 V
LH-SCS parameter settings: Frequency 30-100 Hz, pulse width 100-300 μs, amplitude 0.5-5.0 V

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Numerical scale pain score
Time Frame: Preoperative, postoperative day 7, postoperative day 30, postoperative day 90, postoperative day 180.
An NRS score of 0 indicates no pain; scores ≥1 and <4 indicate mild pain; scores ≥4 and <6 indicate moderate pain; scores ≥7 indicate severe pain.
Preoperative, postoperative day 7, postoperative day 30, postoperative day 90, postoperative day 180.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hamilton Anxiety Rating Scale
Time Frame: Preoperative, postoperative day 7, postoperative day 30, postoperative day 90, postoperative day 180.
A 5-point Likert scale ranging from 0 to 4 is used. A total score ≥29 may indicate severe anxiety; ≥21 indicates definite marked anxiety; ≥14 indicates definite anxiety; a score above 7 may suggest anxiety; a score below 7 indicates no symptoms of anxiety.
Preoperative, postoperative day 7, postoperative day 30, postoperative day 90, postoperative day 180.
Hamilton Depression Rating Scale
Time Frame: Preoperative, postoperative day 7, postoperative day 30, postoperative day 90, postoperative day 180.
A total HAMD score of less than 7 indicates no depression; a score of 7-17 indicates mild depression; a score of 18-24 indicates moderate depression; and a score above 24 indicates severe depression.
Preoperative, postoperative day 7, postoperative day 30, postoperative day 90, postoperative day 180.
Pittsburgh sleep quality index
Time Frame: Preoperative, postoperative day 7, postoperative day 30, postoperative day 90, postoperative day 180.
The total PSQI score ranges from 0 to 20, with lower scores indicating better sleep quality. It is used to assess overall sleep quality.
Preoperative, postoperative day 7, postoperative day 30, postoperative day 90, postoperative day 180.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Li Zhao

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2024

Primary Completion (Estimated)

May 31, 2025

Study Completion (Estimated)

May 31, 2025

Study Registration Dates

First Submitted

April 16, 2025

First Submitted That Met QC Criteria

April 16, 2025

First Posted (Actual)

April 24, 2025

Study Record Updates

Last Update Posted (Actual)

April 30, 2025

Last Update Submitted That Met QC Criteria

April 25, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20241212

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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