UNASSIGNED: Herpes zoster (HZ) and postherpetic neuralgia (PHN) significantly affect patients\' quality of life (QoL). Cultural differences may lead to different patient-reported outcomes across countries. The current study aims to evaluate the detrimental impact of HZ and PHN on QoL in China.
UNASSIGNED: This prospective study was conducted from January 2020 to April 2023. We used the Zoster Brief Pain Inventory (ZBPI) and 5-level EuroQol-5 Dimension (EQ-5D-5L) questionnaire to assess the QoL of HZ and PHN patients. Patients were required to complete the questionnaires at 15, 30, 60, and 90 days after the onset of the HZ rash. Additional questionnaires were administered at 120, 150, and 180 days for those who developed PHN within three months of the rash\'s onset.
UNASSIGNED: A cohort of 633 patients with a median age of 63 years were included in the study. The mean delay from the appearance of the initial HZ rash to the first medical consultation was 5.1 ± 2.8 days. Approximately 30% of the HZ patients (189/633) went on to develop PHN. For patients with HZ who did not progress to PHN, the ZBPI worst pain score and impaired QoL had nearly resolved by day 90 post-rash onset. Conversely, there was no significant improvement in the ZBPI worst pain score and QoL for those with PHN, even by day 180 post-rash onset.
UNASSIGNED: Both HZ and PHN significantly impaired patients\' QoL. However, the impairment caused by PHN was more severe in both intensity and duration.

UNASSIGNED: Solid organ transplant recipients are at high risk for developing severe zoster-associated neuralgia, and the pharmaceutic therapies of pain management for these patients with limited organ function are challenging. Intravenous lidocaine infusion showed positive analgesic effects and is used for the management of neuropathic pain. This case series reports the safety and effectiveness of intravenous lidocaine infusion in the treatment of intractable zoster-associated neuralgia in solid organ transplant recipients.
UNASSIGNED: Five solid organ transplant recipients suffering from refractory zoster-associated neuralgia (numeric rating scale 8-10, despite using high doses of antiepileptic drugs or combined with opioids) were enrolled. Intravenous lidocaine (5 mg/kg ideal bodyweight) was administered over 1.5 h with the monitoring of vital signs. Pain intensity, patient satisfaction, adverse events, typical liver, and kidney function were evaluated. All subjects reported high satisfaction with their treatment and effective pain relief at the 6-month follow-up. One patient experienced short and mild numbness in the mouth and dizziness after the therapy, but no major adverse reactions were reported.
UNASSIGNED: This case series provides evidence that intravenous lidocaine infusion provided effective pain relief as an analgesic treatment option for transplant patients with intractable zoster-associated neuralgia.

BACKGROUND: Herpes zoster is caused by the reactivation of latent varicella infection within the sensory ganglia, caused by the varicella-zoster virus (VZV). The disease is classically characterized by a painful unilateral vesicular eruption. Complications of the disease include herpes zoster ophthalmicus, Ramsay Hunt syndrome, acute retinal necrosis, and post-herpetic neuralgia. In this paper, we discuss the epidemiology, pathogenesis, clinical features, diagnosis, management, and vaccination strategies of herpes zoster and post-herpetic neuralgia.
METHODS: This paper was developed with input from specialists from Singapore\'s public sectors-dermatologists, family physicians, and infectious diseases specialists.
RESULTS: The diagnosis of herpes zoster is clinical and can be aided with laboratory investigations. Early initiation of antivirals, within 72 h of onset, can reduce the severity and duration of the condition and decrease the intensity of pain. In patients with a high risk of post-herpetic neuralgia, early initiation of anticonvulsants or tricyclic antidepressants can be considered. Herpes zoster is highly preventable, with the advent of the recombinant zoster vaccine (RZV) providing an overall vaccine efficacy of 97.2%. Procedures such as epidural blocks and subcutaneous or intracutaneous injections of local anesthetics and steroids can be considered for patients with a high risk of post-herpetic neuralgia to reduce its incidence.
CONCLUSIONS: This article serves as a guideline for clinicians in the diagnosis, investigations, management, and prevention of herpes zoster. With the majority of adults in Singapore currently at risk of developing herpes zoster due to varicella immunization being only introduced in 2020, it is important for clinicians to recognize and manage herpes zoster appropriately.

OBJECTIVE: Ultrasound (US)-guided intercostal nerve block (ICNB) is an easier approach with a very low incidence of complications for different surgeries; nevertheless, only a few studies estimate the effect of ICNB for acute HZ. To explore the US-guided ICNB for management of herpes zoster (HZ)-related acute pain and possible prophylaxis for post-herpetic neuralgia (PHN) taking the conventional thoracic paraverteral block (TPVB) as control.
METHODS: A total of 128 patients with HZ were retrospectively stratified into antiviral treatment (AVT) plus US-guided TPVB (TPVB group), AVT plus US-guided ICNB (ICNB group) or AVT alone (control group) based on the treatment they received. HZ-related illness burden (HZ-BOI) over 30 days after inclusion as the primary endpoint was determined by a severity-by-duration composite pain assessment. Rescue analgesic requirement, health-related quality of life, PHN incidence, and adverse events were also recorded.
RESULTS: Significantly lower HZ-BOI scores within post-procedural 30 days using the area under the curve were reported with TPVB and ICNB compared with the control group: mean difference of 57.5 (p < 0.001) and 40.3 (p = 0.003). No difference was reported between TPVB and ICNB (p = 1.01). Significant greater improvements in PHN incidence, EQ-5D-3L scores, and rescue analgesic requirements were observed during follow-up favoring two trial groups, while comparable between two trial groups. No serious adverse events were observed.
CONCLUSIONS: US-guided ICNBs were as effective as TPVBs for acute HZ. The ICNB technique was an easier and time-efficient approach as opposed to conventional TPVB, which might be encouraged as a more accessible preemptive mean for preventing PHN.

UNASSIGNED: Herpes Zoster in humans is the result of varicella zoster virus (VZV) infection. Injecting rats with varicella zoster virus produces pain similar to herpes zoster \"shingles\" pain in humans. . In a previous study, orofacial pain was induced by injecting the whisker pad of male rats with VZV and the pain response increased after attenuating neurexin 3 (Nrxn3) expression in the central amygdala. Neurons descend from the central amygdala to the lateral parabrachial nucleus and orofacial pain signals ascend to the lateral parabrachial nucleus. GABAergic neurons within the central amygdala regulate pain by inhibiting activity within the lateral parabrachial nucleus. Attenuating Nrxn3 expression in the central amygdala increased GABA release in the lateral parabrachial nucleus suggesting Nrxn3 controls pain by regulating GABA release. Nrxn3 can also control synaptic connections between neurons, and we hypothesized that Nrxn3 knockdown in the central amygdala would reduce the number of GABAergic synaptic connections in the lateral parabrachial nucleus and increase VZV associated pain.
UNASSIGNED: To test this idea, the number of synaptic connections between GABAergic cells of the central amygdala and excitatory or dynorphin positive neurons within the lateral parabrachial nucleus were quantitated after infusion of a virus expressing synaptophysin. Synaptophysin is a synaptic vesicle protein that labels neuronal synaptic connections. These connections were measured in rats with and without whisker pad injection of VZV and knockdown of Nrxn3 within the central amygdala. Orofacial pain was measured using a place escape avoidance paradigm.
UNASSIGNED: GABAergic synaptic connections were reduced in the lateral parabrachial nucleus after Nrxn3 knockdown. Rats with a reduction in the number of connections had an increase in VZV associated orofacial pain. Immunostaining with the pain marker prodynorphin indicated that the reduction in GABAergic connections was primarily associated with prodynorphin positive neurons.
UNASSIGNED: The results suggest Nrxn3 reduces VZV associated orofacial pain, in part, by enhancing synaptic connections between GABA cells of the central amygdala and pain neurons within the lateral parabrachial nucleus.

UNASSIGNED: Herpes zoster (HZ) typically manifests in the acute phase with distinct blisters and severe neuropathic pain. Remarkably, a subset of patients initially presents with only a mild skin rash and moderate pain that gradually intensifies, following a parabolic pattern. Despite being frequently observed in clinical settings, the underlying causes of this trajectory and its potential connection with post-herpetic neuralgia (PHN) remain unclear.
UNASSIGNED: To investigate this phenomenon in-depth, we conducted a meticulous retrospective study involving 529 eligible HZ patients. All these patients sought medical care at the Third Central Hospital of Tianjin, China, between January 2020 and December 2023.
UNASSIGNED: The research identified that 14.6% of the sample (77 patients) experienced pain scores aligning with a parabolic curve. This trend was significantly more prevalent in patients aged 60 and above, accounting for 90.9% of this group, and demonstrated a positive correlation with age. Moreover, 87.0% of these patients had pre-existing medical conditions, highlighting the potential role of comorbidities in influencing the pain trajectory. A concerning 45.5% of patients sought medical attention more than seven days after the onset of symptoms, a delay that could exacerbate neurological damage. Notably, among those following a parabolic pain pattern, 66.2% eventually developed PHN, a considerably higher rate compared to the broader patient population.
UNASSIGNED: We emphasize that healthcare practitioners meticulously assess patients who initially report lower pain scores for high-risk factors potentially leading to parabolic pain increases, including being over 60 years old, having comorbid conditions, and delaying medical consultation beyond seven days from symptom onset. Early implementation of supplementary pain management therapies may mitigate the risk of PHN development and enhance the quality of life for patients. This study furnishes clinicians with a deeper understanding of the variations in HZ-related pain trajectories, promising to improve treatment approaches and prognoses for HZ patients while paving the way for enriched clinical practice in the future.

In Singapore, population aging and rising life expectancy are increasing herpes zoster (HZ) burden, which may be reduced by vaccination. The present study modeled the public health impact of HZ vaccination in Singapore using ZOster ecoNomic Analysis (ZONA) model adapted with Singapore-specific key model inputs, where available. Base case analysis was conducted in adults ≥ 50 years of age (YOA), exploring three vaccination strategies (no vaccination, recombinant zoster vaccine [RZV], zoster vaccine live [ZVL]) under mass vaccination setting (30% coverage). Scenario and sensitivity analyses were performed. Out of 1.51 million adults in 2021 (base case population), 406,513 (27.0%) cases of HZ, 68,264 (4.5%) cases of post-herpetic neuralgia (PHN), and 54,949 (3.6%) cases of other complications were projected without vaccination. RZV was estimated to avoid 73,129 cases of HZ, 11,094 cases of PHN, and 9,205 cases of other complications over the subjects\' remaining lifetime; ZVL would avoid 17,565 cases of HZ, 2,781 cases of PHN, and 1,834 cases of other complications. The number needed to vaccinate to prevent one case of HZ/PHN was lower for RZV (7/41) than ZVL (26/163). Among all five age-stratified cohorts (50-59/60-64/65-69/70-79/≥80 YOA), RZV (versus no vaccination/ZVL) avoided the largest number of cases in the youngest cohort, 50-59 YOA. Results were robust under scenario and sensitivity analyses. Mass vaccination with RZV is expected to greatly reduce the public health burden of HZ among Singapore individuals ≥ 50 YOA. Findings support value assessment and decision-making regarding public health vaccination strategies for HZ prevention in Singapore.
Risk of shingles (herpes zoster) increases with age, especially from 50 years. Shingles is a major public health concern in Singapore, given its rapidly aging population. Vaccination can prevent shingles and reduce its public health burden. Two shingles vaccines are available in Singapore: recombinant zoster vaccine (RZV) since 2021, zoster vaccine live (ZVL) since 2008. To understand the value of preventing shingles via vaccination, this study assessed the public health impact of shingles vaccination. Three vaccination strategies (no vaccination, vaccination with RZV, vaccination with ZVL) were compared in 1.51 million Singapore adults aged 50 years and above. Without vaccination, public health burden of shingles would be high; an estimated 406,513 (27.0%) would have shingles, 68,264 (4.5%) would have shingles-related long-term nerve pain, 54,949 (3.6%) would have other shingles-related complications, and 17,762 (1.2%) would be hospitalized due to shingles. Shingles vaccination could reduce this public health burden: RZV avoided 73,129 cases of shingles, 11,094 cases of shingles-related long-term nerve pain, 9,205 cases of other shingles-related complications, and 2,827 hospitalizations due to shingles, which was 4–6 times that avoided with ZVL (shingles: 17,565; shingles-related long-term nerve pain: 2,781; other shingles-related complications: 1,834; hospitalizations due to shingles: 484). Shingles vaccination for adults aged 50 years and above, especially early vaccination from 50–59 years, could reduce its public health burden more than vaccination at later ages and contribute toward healthy aging, preventive care, and the Healthier SG initiative. Results support local public health value assessments and decision-making for shingles prevention.

Chronic varicella zoster virus (VZV) infection induced neuroinflammatory condition is the critical pathology of post-herpetic neuralgia (PHN). The immune escape mechanism of VZV remains elusive. As to mice have no VZV infection receptor, herpes simplex virus type 1 (HSV-1) infection is a well established PHN mice model. Transcriptional expression analysis identified that the protein arginine methyltransferases 6 (Prmt6) was upregulated upon HSV-1 infection, which was further confirmed by immunofluorescence staining in spinal dorsal horn. Prmt6 deficiency decreased HSV-1-induced neuroinflammation and PHN by enhancing antiviral innate immunity and decreasing HSV-1 load in vivo and in vitro. Overexpression of Prmt6 in microglia dampened antiviral innate immunity and increased HSV-1 load. Mechanistically, Prmt6 methylated and inactivated STING, resulting in reduced phosphorylation of TANK binding kinase-1 (TBK1) and interferon regulatory factor 3 (IRF3), diminished production of type I interferon (IFN-I) and antiviral innate immunity. Furthermore, intrathecal or intraperitoneal administration of the Prmt6 inhibitor EPZ020411 decreased HSV-1-induced neuroinflammation and PHN by enhancing antiviral innate immunity and decreasing HSV-1 load. Our findings revealed that HSV-1 escapes antiviral innate immunity and results in PHN by upregulating Prmt6 expression and inhibiting the cGAS-STING pathway, providing novel insights and a potential therapeutic target for PHN.

UNASSIGNED: Herpes zoster (HZ) and post-herpetic neuralgia (PHN) cause considerable morbidity, especially in elderly adults, but the burden is under-recognized in mainland China.
UNASSIGNED: We conducted a case registry and follow-up study of HZ in Miyun District, Beijing from January 1, 2017 through December 31, 2018. Registered HZ cases were followed-up for pain to 365 days. The first 50 patients with HZ in each age group (≤14, 15-29, 30-39, 40-49, 50-59, 60- 69, 70-79, ≥80 years) and all those with PHN completed the EuroQoL five dimensions questionnaire (EQ-5D) to evaluate health-related quality of life (HRQoL) in patients with HZ and PHN. Ratings using the EQ-5D dimensions, visual analogue scale (VAS), health utility score (HUS) and quality-adjusted life years (QALYs) lost were compared among age groups.
UNASSIGNED: In total, 2008 patients with HZ were followed for a median 22 days (interquartile range[IQR] = 20-90), with an estimated incidence of 4.39 per 1000 person-years. We identified 122 (6.08 %) PHN cases. The median age of patients with PHN (65 years, IQR = 55-71) was older than that of patients with HZ (54 years, IQR = 43-64) (P < 0.001). The median duration of pain was 170 days (IQR = 144-355.5) for PHN and 15 days (IQR = 9-25) for HZ. All 95 patients with PHN and 319 sampled patients with HZ completed the EQ-5D survey. The median QALY loss of HZ increased from 0.004 (IQR = 0.001-0.02) in patients 50-59 years old to 0.02 (IQR = 0.01-0.06) in those ≥ 80 years old (P < 0.01). After weighting for age, the mean QALY loss per HZ case was estimated at 0.02 (standard deviation [SD] 0.04). The mean QALY loss per PHN case was 0.13 years (SD 0.12).
UNASSIGNED: HZ and PHN caused a substantial burden, especially among adults aged ≥ 50 years in Miyun District, Beijing, China. Vaccination should be considered to alleviate the burden of this painful disease.

BACKGROUND: Post herpetic neuralgia (PHN) is a chronic neuropathic pain syndrome which presents after an episode of herpes zoster caused by the reactivation of varicella zoster virus. Conservative treatment starts with pharmacological measures using Anti-epileptics and Antidepressants. Some patients also respond well to epidural steroid injections too, but the effect is usually short lasting. Dorsal Root Ganglion Stimulator (DRG-S) has recently been suggested as a new treatment modality for PHN due to its selective targeting of the pathophysiologic focus.
METHODS: We are reporting three cases, who were suffering from neuropathic pain after an episode of herpes zoster. Pain and pain related suffering scores were high, even with multiple antiepileptics and opioid medications. They underwent DRG-S implant and appreciated more than 50% reduction of their pain score, meaningful reduction in the dose of medications along with significant improvement of their general well being measured using Generalized Anxiety Disorder Questionnaire (GAD-7), pain disability index (PDI), and 9 Question Patient Health Questionnaire (PHQ-9). To our knowledge this is the first report on DRG stimulator from the Middle East Region.
CONCLUSIONS: DRG-S has potential to be a preferable treatment option in patients with refractory PHN and acts as a specific targeted therapy in the treatment of these patients.