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Zoster-associated neuralgia (ZAN) is a neuropathic pain caused by the reactivation of the varicella-zoster virus (VZV). The global annual incidence is 3-5 per 1,000 individuals, while in China, it is 4.89 per 1,000 individuals, increasing with age. The mechanisms of ZAN involve neuroinflammation, peripheral/central sensitization, and other factors, leading to anxiety, depression, and severe declines in quality of life. Treatment of ZAN remains challenging. Spinal cord stimulation (SCS) alleviates pain through multiple mechanisms, including the "gate control theory," modulation of neurotransmitters (e.g., gamma-aminobutyric acid), suppression of neuroinflammation (reducing IL-1β and TNF-α), and promotion of autophagy. However, traditional low-frequency SCS (30-100 Hz) has limitations such as incomplete pain coverage, diminished efficacy over time, and side effects like paresthesia (e.g., tingling sensations).
High-frequency SCS (HF-SCS, 1000 Hz) provides pain relief without paresthesia. Studies suggest its superiority over traditional SCS; for example, Duarte et al. reported that 39% of HF-SCS patients achieved ≥50% pain relief at 3 months (vs. 29% in the traditional SCS group), with 66% of patients preferring HF-SCS. However, clinical data on HF-SCS for ZAN are scarce, and no related studies exist in China. This study compares the efficacy of short-term high-frequency (1 kHz) SCS with traditional low-frequency SCS in ZAN treatment. By evaluating pain relief (NRS scores), improvements in anxiety/depression (HADS), sleep quality (PSQI), patient experience, and complication rates, the research aims to assess the safety and efficacy of short-term HF-SCS for ZAN, potentially offering a novel therapeutic option for patients.
Full description
Zoster-associated neuralgia (ZAN) refers to neuropathic pain following HZ infection. Based on disease duration, ZAN is classified into three stages: acute herpetic neuralgia (AHN, <1 month), subacute herpetic neuralgia (SHN, 1-3 months), and postherpetic neuralgia (PHN, >3 months). The global annual incidence of HZ is approximately 3-5 per 1,000 individuals, with higher rates in those aged ≥50 years and in females . In China, the annual incidence is 4.89 per 1,000 individuals, increasing with 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 . Neurotransmitter-wise, SCS enhances γ-aminobutyric acid (GABA) release, reduces glutamate levels, amplifies endogenous opioid effects, and activates the endocannabinoid system, rebalancing spinal dorsal horn signaling to inhibit 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. Thomson et al. demonstrated in a crossover study that 1-10 kHz SCS provided comparable pain relief without paresthesia, with 1 kHz being more energy-efficient. Jo et al. reported a case of refractory neuropathic pain after spinal cord injury where 1 kHz HF-SCS significantly reduced pain scores over 6 months. While preclinical and clinical studies support HF-SCS safety and efficacy , its superiority over low-frequency SCS remains debated. North et al. found 1 kHz SCS outperformed traditional SCS in pain scores (NRS), functional improvement (ODI), and patient satisfaction (PGIC). Duarte et al. reported 39% of HF-SCS patients achieved ≥50% pain relief at 3 months (vs. 29% with traditional SCS), with 66% preferring HF-SCS after 12 months (NRS: 7.3±1.1 to 4.0±2.1). Conversely, Kriek et al. found similar efficacy across frequencies (40 Hz, 500 Hz, 1200 Hz), highlighting the need for further research on optimal parameters and disease-specific mechanisms.
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.
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Inclusion Criteria:
Exclus(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 Criteria:
74 participants in 2 patient groups
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梨 赵
Data sourced from clinicaltrials.gov
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