Herpes zoster (HZ) is a disorder of nerve tissue with both acute and long-term manifestations. Zoster-associated neuralgia (ZAN) is found in patients with HZ and is the main reason for them to seek medical assistance. It is associated with a significant reduction in health-related quality of life (HRQoL). Neuropathic pain belongs to the category of "girdling fire cinnabar" in traditional Chinese medicine (TCM).
HZ stems from reactivation of an endogenous varicella-zoster virus (VZV). Primary infection results in varicella. The virus invades and establishes latency within the dorsal root ganglia of sensory or cranial nerves for years. When the latent virus replicates and spreads under immunosuppression status, the body may subsequently develop HZ. It is characterized as a vesicular rash with dermatomal distribution and neuropathic pain.
The course of HZ can be divided into four stages: pre-eruptive, acute, subacute, and postherpetic neuralgia (PHN). ZAN appears to occur in each stage. In the pre-eruptive stage, the sign is usually localized pain without tenderness or visible skin change. In the acute eruptive stage, a blistering rash appears and develops. The vesicles continue to erupt and eventually dry out. Neuropathic pain is typically severe. Persistent or recurring pain lasts for more than four weeks in subacute HZ infection. The patient may experience a continuous burning sensation in the affected areas. When pain lasts for over three months, the long-term condition is known as PHN. It is the most frequent complication of HZ. This pain is incapacitating. Effective pain management is crucial.
TCM has been widely used in the treatment of ZAN. Practical approaches involve orally administered medicinal formulas, medicinal powder, acupuncture, and moxibustion therapies. It is relatively simple and provides quick effective relief. TCM can hasten the resolution of pain and decrease the incidence, duration, and severity of chronic pain. Furthermore, TCM formulas act as an antiviral agent to combat the pathological condition. At the onset of HZ infection, earlier TCM interventions lead to greater benefits. The use of TCM could achieve the purpose of treating both the symptoms and root causes and improve the prognosis and life quality in patients with ZAN.
From the perspective of TCM, ZAN is attributed to factors, such as heat, dampness, and toxin invading the liver channel, or energy stuck and blood not smoothly flowing inside the body. These abnormalities will be reflected in various ways that can be observed. TCM has unique efficacy indicators for evaluating ZAN. TCM doctors will conduct a multifaceted evaluation including the patient's tongue, complexion, pulse, and meridians as well as changes in sleep and diet.
TCM possesses certain advantages in the treatment of ZAN. However, there has been a risk of inconsistency and outcome reporting bias between clinical trials. The need for better evidence synthesis and direct comparisons across research studies is a challenge.
Therefore, the effective strategy for minimizing the negative impact of these problems is to establish a Core Outcome Set (COS) of TCM on ZAN at different clinical stages. This minimum set is designed to meet the needs of clinical studies exploring TCM’s approaches to ZAN relief.
Neuropathic pain varies greatly under different conditions. In the COMET database, existing neuropathic pain-related COS for clinical studies often focus on specific diseases, such as diabetic neuropathy (https://www.comet-initiative.org/Studies/Details/2461) and trigeminal neuralgia (https://www.comet-initiative.org/Studies/Details/1123). Significant work has been conducted on COS uptake studies. These entailed determining the frequency of use of the core outcome domains in burning mouth syndrome (https://www.comet-initiative.org/Studies/Details/1368) and neuropathic pain conditions (https://www.comet-initiative.org/Studies/Details/2420). Neither ongoing nor completed COS registration information on TCM for neuropathic pain associated with HZ has been found. ZAN can have a significant negative impact on the functional status of affected individuals. Therefore, it is of great value to develop a COS for clinical trials of TCM for ZAN disease, concentrating on the assessment of changes in symptoms and prognosis.
The main objective of this study is to establish the COS for future TCM clinical trials of herpes zoster-associated neuralgia.
Zongda Jin [1,2] (the principal investigator), Junyi Wang [2], Yuanyuan Wu [1,2] (supervisor)
1. The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China;
2. The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
Disease Category: Neurology
Disease Name: Herpes zoster-associated neuralgia
Age Range: 18 - 100
Sex: Either
Nature of Intervention: Traditional Chinese Medicine
- Clinical experts
- Consumers (caregivers)
- Consumers (patients)
- Methodologists
- Researchers
- COS for clinical trials or clinical research
- COS for practice
- Consensus conference
- Delphi process
- Interview
- Systematic review
To develop the outcome set, the advanced approach consists of four interlinked phases. First, extensive systematic reviews of the literature on the treatment of ZAN utilizing TCM identify the relevant effective outcomes. Second, qualitative research is conducted. Semi-structured interview on patients, caregivers, and doctors’ perspectives aims to probe deeply into outcomes of interest. A comprehensive inventory of outcomes is generated. Next, a two-round Delphi survey is undertaken to rate the importance of outcome measures and gather the options of key stakeholders including clinicians, researchers, methodologists, patients, and caregivers. Finally, a consensus conference with stakeholder consultation is held to form the outcome set for the effect of TCM on ZAN.
Ethics and dissemination
The study was reviewed and approved by the institutional ethics committee of The Third Affiliated Hospital of Zhejiang Chinese Medical University (ZSLL-KY-2024-071-01). The findings will be shared in peer-reviewed journals.