HSV-1 reactivation results in post-herpetic neuralgia by upregulating Prmt6 and inhibiting cGAS-STING.

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.

Dorsal root ganglion stimulator-A targeted therapy for post-herpetic neuralgia: The Middle East Experience.

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. CASE SERIES: 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. CONCLUSION: 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.

Spinal abscess after epidural block and radiofrequency ablation in a patient with post-herpetic neuralgia.

A 67-year-old man was admitted due to a two-week history of pain on the right side of his chest, upper back, and armpit, and progressive lower-limb weakness. The results of Magnetic Resonance Imaging and colour ultrasound supported the diagnosis of spinal abscess. The patient underwent a series of debridement and antibacterial treatments, but no obvious recovery of muscle strength was observed. This case highlights the potentially serious complications of invasive analgesic therapy.

Efficacy of local anaesthetic and steroid combination in prevention of post-herpetic neuralgia: A meta-analysis.

Objective: The objective was to provide synthesized evidence on the efficacy of local anaesthetics and steroid injections for prevention and management of PHN, compared to the standard treatment using anti-viral and analgesic medications. The primary outcomes of interest were incidence of PHN and duration of neuralgic pain. Methods: Comprehensive searches were done systematically through PubMed, Scopus, Cochrane Central Register of Controlled Trials and Google scholar databases. Randomized controlled trials that compared the efficacy of local anaesthetics and steroid injections for preventing and managing PHN were included for this meta-analysis. A comprehensive search was done for papers published until 15th July 2021. Results: A total of 10 RCTs were included in the meta-analysis. In the overall pooled analyses, compared to standard care/placebo, those receiving a combination of local anaesthetic and steroid injection had 55% lower risk of PHN at 3 months from onset of rash (RR 0.45; 95% CI, 0.29; 0.70). Out of the different modes of intervention delivery i.e., intravenous, subcutaneous and nerve block, maximum beneficial effect in reducing the incidence of PHN was noted in nerve block (RR 0.55; 95% CI, 0.34, 0.89). Conclusions: The meta-analysis provides some evidence to support the use of combined local anaesthetic and steroids in reducing risk of post-herpetic neuralgia and duration of neuralgic pain in patients with herpes zoster rash.

Heparan sulfate 3-O-sulfotransferase 4 is genetically associated with herpes zoster and enhances varicella-zoster virus-mediated fusogenic activity.

Acute pain that is associated with herpes zoster (HZ) can become long-lasting neuropathic pain, known as chronic post-herpetic neuralgia (PHN), especially in the elderly. HZ is caused by the reactivation of latent varicella-zoster virus (VZV), whereas PHN is not attributed to ongoing viral replication. Although VZV infection reportedly induces neuronal cell fusion in humans, the pathogenesis of PHN is not fully understood. A genome-wide association study (GWAS) revealed significant associations between PHN and the rs12596324 single-nucleotide polymorphism (SNP) of the heparan sulfate 3-O-sulfotransferase 4 (HS3ST4) gene in a previous study. To further examine whether this SNP is associated with both PHN and VZV reactivation, associations between rs12596324 and a history of HZ were statistically analyzed using GWAS data. HZ was significantly associated with the rs12596324 SNP of HS3ST4, indicating that HS3ST4 is related to viral replication. We investigated the influence of HS3ST4 expression on VZV infection in cultured cells. Fusogenic activity after VZV infection was enhanced in cells with HS3ST4 expression by microscopy. To quantitatively evaluate the fusogenic activity, we applied cytotoxicity assay and revealed that HS3ST4 expression enhanced cytotoxicity after VZV infection. Expression of the VZV glycoproteins gB, gH, and gL significantly increased cytotoxicity in cells with HS3ST4 expression by cytotoxicity assay, consistent with the fusogenic activity as visualized by fluorescence microscopy. HS3ST4 had little influence on viral genome replication, revealed by quantitative real-time polymerase chain reaction. These results suggest that HS3ST4 enhances cytotoxicity including fusogenic activity in the presence of VZV glycoproteins without enhancing viral genome replication.

Vaccination for quality of life: herpes-zoster vaccines.

Current vaccination policy in most high-income countries aims to counteract the decline in cell-mediated immunity to varicella zoster virus that occurs with advancing age or immunosuppression. The aim of this review was to describe the burden of illness associated with herpes zoster (HZ) and post-herpetic neuralgia (PHN) risks and their impact on the social and common life in infected people. The effectiveness/efficacy and cost effectiveness of the immunization strategy will be presented through the review of the literature relevant to the live attenuated HZ vaccine (ZLV) licensed in 2006 and the recombinant HZ vaccine (RZV). The latter has very recently been approved to protect aged people aged ≥ 50 years against HZ morbidity including its complications, and associated health-care costs. Finally, this review also provides data with respect of precautions of using and safety of ZVL and RVZ.

Burst Stimulation of the Thoracic Spinal Cord near a Cardiac Pacemaker in an Elderly Patient with Postherpetic Neuralgia: A Case Report.

New developments in spinal cord stimulation (SCS) have improved the treatment of patients with chronic pain. Although the overall safety of modern SCS has been established, there are no published reports regarding safety considerations when implanting a burst-mode spinal cord stimulator in patients with permanent cardiac pacemakers (PCPs). An 80-year-old man with a complete atrioventricular block implanted with a PCP was considered as a candidate for burst-mode SCS due to well-established postherpetic neuralgia (>180 days after rash). Cardiac monitoring during the burst-mode spinal cord stimulator trial and insertion did not indicate any interference. After the insertion of the burst-mode spinal cord stimulator, the patient showed functional improvement and significant pain relief. The safety of traditional tonic-mode SCS in patients with PCP has been previously reported. This is the first case report describing the safe and effective use of burst-mode SCS in a patient with PCP.

Dorsal root ganglion stimulation for refractory post-herpetic neuralgia.

Post-herpetic neuralgia is a chronic neuropathic pain disorder that is the sequela of the varicella zoster virus reactivation in the dorsal root ganglion. A variety of treatment modalities have been implemented, but pharmacologic treatments are often limited due to side effects and interventional procedures have yielded mixed results without promising long-term benefits being consistently seen. A dorsal root ganglion stimulator for treatment of post-herpetic neuralgia is a novel treatment option as it is able to specifically target the area affected. We present 3 patients who underwent implantation of permanent dorsal root ganglion stimulators and had a greater than 50% decrease in scoring on numerical rating scale (NRS) up to 18 months post-procedure and significantly reduced analgesic requirements.

Study on the related factors of post-herpetic neuralgia in hospitalized patients with herpes zoster in Sichuan Hospital of Traditional Chinese Medicine based on big data analysis.

Although various factors were reported to be related to post-herpetic neuralgia (PHN), studies based on adequate and comprehensive data were absent. Data was extracted from cases of hospitalized patients with herpes zoster in dermatology department, Sichuan hospital of traditional Chinese medicine range from December, 2011 to February, 2018, and then cleaned to build prediction model with TREENET algorithms. Following evaluated the prediction model by ROC and confusion matrix, variables importance ranking and variables dependency analysis were performed, resulting in the importance ranking of factors for PHN and the dependency between factors and PHN. Based on strict inclusion and exclusion criteria, 1303 (571 PHN and 732 normal controls) cases and 2958 indicators were selected. Model evaluation showed high ROC value (training sample = 0.985, test samples = 0.752) and high accuracy value (70.27%), which indicated that the model was predictive. After variables importance ranking and variables dependency analysis, 62 variables in the model were associated with the occurrence of PHN. Our study identified 62 variables related to PHN and revealed that various variables were the important risk factors for PHN, including age, MCHC, sodium and UA.

Role of low-level laser therapy in post-herpetic neuralgia: a pilot study.

The aim of the present study was to investigate the influence of low-level laser radiation at a wavelength of 650 nm for treating post-herpetic neuralgia, an extremely painful condition which frequently occurs severely in old age and may persist for years with no predictable course. In total, fifteen patients were included in the present study, out of which 8 were females and 7 were males aged between 42 and 82 years. All patients were treated through 16 sessions for 8 weeks, and pain scoring was done on a visual analogue scale and statistical analysis was made for comparison before and after treatments. The final pain score was 0 in 11 patients although their initial pain score was severe in 8 and moderate in 3 patients. In three patients, pain reduced to mild intensity (2-3), and in one, the final pain score was 4 on the visual analogue scale. Patients treated during the present study have not complained for recurrence of pain or any other abnormality even after many months since completion of the therapy. Overall, low-level laser therapy (LLLT) proved itself an excellent therapeutic modality for the relief of pain in post-herpetic neuralgia patients, which may replace pain management medicines in future.

Pilot Study in Temporary Peripheral Nerve Stimulation in Oncologic Pain.

OBJECTIVES: Temporary, percutaneous peripheral nerve stimulation (PNS) has been shown to provide analgesia for acute postoperative pain, postamputation pain, and low back pain. The implanted device stimulates the neural target for up to 60 days at which point the leads are extracted. Patients have demonstrated prolonged analgesia continuing after extraction of the leads. The purpose of this case series is to demonstrate peripheral neural targets that could feasibly be used to treat various pain syndromes prevalent in the oncologic population. MATERIALS AND METHODS: A temporary, percutaneous PNS was implanted under ultrasound guidance in 12 oncologic chronic pain patients seen in an outpatient pain clinic who had failed medical and/or interventional management. The device was implanted for up to 60 days. Clinical progress of pain and functional capacity was monitored through regular clinical visits. RESULTS: The case series presents seven successful cases of implementation of the PNS to treat oncologic pain. Three of these cases demonstrate targeting of proximal spinal nerves to treat truncal neuropathic pain and lumbar radicular pain. The four remaining cases demonstrate successful targeting of other peripheral nerves and brachial plexus. We also share five failed cases without adequate pain relief with PNS. CONCLUSIONS: PNS has potential uses in the treatment of oncologic pain. Further high-quality studies should be designed to further elucidate use of the PNS to treat oncologic pain.

A Rare Manifestation of Herpes Zoster: A Case Report.

Herpes zoster has an incidence of 350,000 cases per year in the United States. The involvement of the foot and ankle is rare. Most surgeons are not aware of this disease as a cause of extremity pain, its manifestation, and the treatment options. Post-herpetic neuralgia is a common sequela of herpes zoster and can be prevented with prompt treatment. In this article, we present a case of a 53-year-old female with right heel pain secondary to herpes zoster.

Persistence of pregabalin treatment in Taiwan: a nation-wide population-based study.

BACKGROUND: Pregabalin is approved for the treatment of neuropathic pain, fibromyalgia, and seizure disorders, although the pivotal trials were mostly carried out in Europe or North America. The prescribing patterns among different indications in Asia have rarely been explored. METHODS: This was a population-based retrospective cohort study based on the National Health Insurance Research Database in Taiwan. Prescriptions of pregabalin were identified, and data regarding demographics, indications, co-existing diagnoses, and concomitant medications were extracted. Pregabalin users were followed for at least one year, and factors associated with persistence at one year were determined by using multivariate logistic regression analysis. RESULTS: Between June 2012 and December 2016, 114,437 pregabalin users (mean age 60.7 ± 15.4 years, 57.8% female) were identified. The indications included post-herpetic neuralgia (PHN) (30.5%), musculoskeletal diseases other than fibromyalgia (21.2%), fibromyalgia (18.4%), diabetic peripheral neuropathic pain (DPNP) (11.7%) and epilepsy (2.9%). Overall, 62.5% and 6.4% of patients achieved a maximum dose of ≥150 and ≥ 300 mg/day, respectively. The median duration of persistent pregabalin use was 28 days (interquartile range 14-118 days). The one-year persistence rate was 12.1%, and the indications associated with the highest and lowest persistence rates were epilepsy (42.4%) and PHN (6.1%), respectively. Male gender (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.09-1.18), older age (OR 1.01 per year, 95% CI 1.01-1.01), indications other than PHN, especially epilepsy (OR 8.04, 95% CI 7.33-8.81, PHN as reference), and a higher initial dose (OR 1.12 per 75 mg, 95% CI = 1.10-1.15) were associated with persistence at one year, whereas the initial concomitant use of antiviral agents decreased the likelihood (OR 0.41, 95% CI 0.35-0.47). CONCLUSIONS: Pregabalin prescriptions for pain disorders were limited to short-term use, which is consistent around the world. However, the average prescribed dose in Taiwan was lower than those in Western countries, and was frequently below the recommended ranges. Potential causes included the duration of natural history of PHN, and off-label prescriptions for pain in acute herpes zoster, rather than PHN, as well as intolerance to the side effects.

Burst or Conventional Peripheral Nerve Field Stimulation for Treatment of Neuropathic Facial Pain.

BACKGROUND: Trigeminal Neuropathic Pain (TNP) is a chronic facial pain syndrome caused by a lesion or disease affecting one or more branches of the trigeminal nerve. It may, for example, result from accidental injury to a branch of the trigeminal nerve by trauma or during surgery; it may also be idiopathic. TNP is typically constant, in contrast to most cases of the commoner trigeminal neuralgia. In some cases, pain may be refractory to pharmacological treatment. Peripheral nerve field stimulation is recognized as an effective minimally invasive surgical treatment option for this debilitating condition. To date, stimulation has used conventional tonic waveforms, which generate paraesthesia in the stimulated area. This is the first report of the use of paraesthesia-free burst pattern stimulation for TNP. METHODS: Seven patients were treated at the John Radcliffe Hospital for TNP from 2016 to 2018. Mean duration of preoperative symptoms was five years. All patients had exhausted pharmacological measures to limited effect. The initial three patients had tonic stimulation with the subsequent four having burst stimulation. Outcome was assessed using the numeric pain rating scale preoperatively and postoperatively at three and six months and one year. Side-effects and complications were also assessed as well as reduction in analgesic medication use. RESULTS: All patients achieved pain reduction of at least 50% at 6 months (range 50-100%, mean 81%, p = 0.0082). Those in the burst stimulation group were paraesthesia free. One patient developed a postoperative infection for which the system had to be removed and is awaiting reimplantation. There were no other complications in either group. CONCLUSION: Burst stimulation conferred similar pain control to tonic stimulation in our small cohort, and there were similar reductions in pain medication use. An additional benefit of burst stimulation is freedom from paraesthesia. Larger scale studies are needed to further evaluate burst stimulation and compare its efficacy with that of tonic stimulation.

Ultrasound-Guided Cervical Nerve Root Block for the Treatment of Acute Cervical Herpes Zoster: A Randomized Controlled Clinical Study.

OBJECTIVES: To evaluate the efficacy and safety of ultrasound-guided cervical nerve root block (CRB) on acute pain and its preventive effects on post-herpetic neuralgia (PHN) in patients with cervical herpes zoster (HZ). METHODS: 140 recruited participants were randomized 1:1 to receive ultrasound-guided CRB with either mixed drug liquid (treatment group) or similar looking placebo (placebo group). All patients received a 7-day course of oral antiviral treatment, pregabalin, and analgesics as needed. The primary efficacy was assessed on the basis of HZ burden of illness (HZ-BOI) scores over 30 days (BOI-30AUC ). Secondary outcomes included HZ-BOI scores through 30 to 90 days (BOI-30-90AUC ) and 90 to 180 days (BOI-90-180AUC ), quality of life (QoL) outcomes, concomitant analgesic consumption, and the incidence of PHN. Adverse events were recorded to evaluate safety. RESULTS: The BOI-30AUC values were 92.55 and 112.72 for the treatment and placebo groups, respectively (P < 0.01). Both the BOI-30-90AUC and BOI-90-180AUC in the treatment group were lower than those in the placebo group (P < 0.01). The incidence of PHN at 90 days was significantly less than that at 180 days in the treatment group (P = 0.036). A better improvement in QoL was found in the treatment group (P < 0.05). There was a greater decrease in analgesic use in the treatment group as compared to the placebo group (P < 0.05). No serious adverse events were observed. CONCLUSIONS: Ultrasound-guided CRB represented an early intervention and preventive strategy to reduce the BOI due to acute HZ in the cervical dermatome region, and might be feasible to reduce the incidence of PHN.

Cost-effectiveness of vaccination of immunocompetent older adults against herpes zoster in the Netherlands: a comparison between the adjuvanted subunit and live-attenuated vaccines.

BACKGROUND: The newly registered adjuvanted herpes zoster subunit vaccine (HZ/su) has a higher efficacy than the available live-attenuated vaccine (ZVL). National decision-makers soon need to decide whether to introduce HZ/su or to prefer HZ/su above ZVL. METHODS: Using a Markov model with a decision tree, we conducted a cost-effectiveness analysis of vaccination with HZ/su (two doses within 2 months) or zoster vaccine live (ZVL) (single dose, or single dose with a booster after 10 years) for cohorts of 50-, 60-, 70- or 80-year-olds in the Netherlands. The model was parameterized using vaccine efficacy data from randomized clinical trials and up-to-date incidence, costs and health-related quality of life data from national datasets. We used a time horizon of 15 years, and the analysis was conducted from the societal perspective. RESULTS: At a coverage of 50%, vaccination with two doses of HZ/su was estimated to prevent 4335 to 10,896 HZ cases, depending on the cohort age. In comparison, this reduction was estimated at 400-4877 for ZVL and 427-6466 for ZVL with a booster. The maximum vaccine cost per series of HZ/su to remain cost-effective to a willingness-to-pay threshold of €20,000 per quality-adjusted life year (QALY) gained ranged from €109.09 for 70-year-olds to €63.68 for 50-year-olds. The cost-effectiveness of ZVL changed considerably by age, with corresponding maximum vaccine cost per dose ranging from €51.37 for 60-year-olds to €0.73 for 80-year-olds. Adding a ZVL booster after 10 years would require a substantial reduction of the maximum cost per dose to remain cost-effective as compared to ZVL single dose. Sensitivity analyses on the vaccine cost demonstrated that there were scenarios in which vaccination with either HZ/su (two doses), ZVL single dose or ZVL + booster could be the most cost-effective strategy. CONCLUSIONS: A strategy with two doses of HZ/su was superior in reducing the burden of HZ as compared to a single dose or single dose + booster of ZVL. Both vaccines could potentially be cost-effective to a conventional Dutch willingness-to-pay threshold for preventive interventions. However, whether HZ/su or ZVL would be the most cost-effective alternative depends largely on the vaccine cost.

Neuropathic pain: A patient-centred approach to measuring outcomes.

BACKGROUND: Neuropathic pain (NP) is a complex, chronic pain state initiated by a primary lesion or dysfunction of the nervous system and presents as a variety of symptoms across multiple disease states. OBJECTIVE: To develop a patient-centred conceptual model of symptoms and impacts in subjects with diabetic peripheral neuropathy (DPN) or post-herpetic neuralgia (PHN) that can inform the measurement strategy in clinical trials. METHOD: Thirty subjects with DPN or PHN participated in in-person interviews which were performed until saturation was achieved. Transcripts were analysed in ATLAS.ti. RESULTS: Interviews were completed with DPN subjects (United States, n = 10; Japan, n = 10) and PHN subjects (United States, n = 5; Japan, n = 5). Numbness and tingling were frequently reported symptoms in the DPN population while itchiness and hypersensitivity were predominant in PHN. Both populations experienced burning and ache/soreness with similar frequency. DPN subjects experienced pain primarily in their lower extremity (eg feet, ankles), while PHN subjects experienced pain primarily in the chest and back. Impacts reported by DPN subjects included difficulty walking, sleep disturbance and climbing stairs. Impacts in PHN subjects included sleep disturbance, avoidance of physical contact, being angry/frustrated and being sad/depressed. Overall, concepts in Japan were not qualitatively different from the United States. Conceptual models of NP were generated based on the concepts elicited. CONCLUSIONS: This research highlights core concepts to measure from the patient's perspective. Moreover, it enables the assessment of existing measures, the possible modification of these measures, or if a new NP measure with improved sensitivity and responsiveness is merited.

A Novel Minimally Invasive Wireless Technology for Neuromodulation via Percutaneous Intercostal Nerve Stimulation for Post-Herpetic Neuralgia: A Case Report with Short-Term Follow-up.

BACKGROUND: Peripheral nerve stimulation of primary afferent neurons provides control of localized chronic pain. This technique applies permanent electrical stimulation at the target area via a minimally invasive, subcutaneous placement of an electrode. OBJECTIVE: To assess the analgesic effects of minimally invasive wireless neuromodulation in the treatment of chronic intractable pain secondary to post-herpetic neuralgia. CASE SUMMARY: A 78-year-old man presented with severe intractable post-herpetic neuralgic pain. He was known to have non-Hodgkin's lymphoma under remission following treatment with chemotherapy and stem cell transplantation, twice. He also developed steroid-induced diabetes mellitus during this treatment. In view of his compromised immune status, he was deemed a suitable candidate for our minimally invasive neuromodulation technology. Two subcutaneous electrodes were placed on the right-hand side of the trunk, 10 cm medial and parallel to the spinous process at the level of T7-T8 under fluoroscopic guidance along the T7 intercostal nerve. The external transmitter was worn with a belt over a single layer of clothing and used to transmit power to the stimulator. The entire procedure required only a small incision for the introduction of the electrode placement. RESULTS: After an uneventful procedure, the pain score decreased from 8 to 3, with a reduction in pain medication. The EuroQol Five Dimensions Questionnaire scores were 0.102 before the trial, 0.630 at 1 month, and 0.576 at 3 months. CONCLUSIONS: Subcutaneous placement of electrodes with our minimally invasive technique and wireless neuromodulation technology was safe and effective. Significant improvements in pain relief ensued, and no further adverse events had been reported at the end of 3 months' follow-up.

Effectiveness and Duration of Protection Provided by the Live-attenuated Herpes Zoster Vaccine in the Medicare Population Ages 65 Years and Older.

Background: Tens of millions of seniors are at risk of herpes zoster (HZ) and its complications. Live attenuated herpes zoster vaccine (HZV) reduces that risk, although questions regarding effectiveness and durability of protection in routine clinical practice remain. We used Medicare data to investigate HZV effectiveness (VE) and its durability. Methods: This retrospective cohort study included beneficiaries ages ≥65 years during January 2007 through July 2014. Multiple adjustments to account for potential bias were made. HZV-vaccinated beneficiaries were matched to unvaccinated beneficiaries (primary analysis) and to HZV-unvaccinated beneficiaries who had received pneumococcal vaccination (secondary analysis). HZ outcomes in community and hospital settings were analyzed, including ophthalmic zoster (OZ) and postherpetic neuralgia (PHN). Results: Among eligible beneficiaries (average age 77 years), the primary analysis found VE for community HZ of 33% (95% CI: 32%-35%) and 19% (95% CI: 17%-22%), for the first 3, and subsequent 4+ years postvaccination, respectively. In the secondary analysis, VE was, respectively, 37% (95% CI: 36%-39%) and 22% (95% CI: 20%-25%). In the primary analysis, VE for PHN was 57% (95% CI: 52%-61%) and 45% (95% CI: 36%-53%) in the first 3 and subsequent 4+ years, respectively; VE for hospitalized HZ was, respectively, 74% (95% CI: 67%-79%) and 55% (95% CI: 39%-67%). Differences in VE by age group were not significant. Conclusions: In both the primary and secondary analyses, HZV provided protection against HZ across all ages, but effectiveness declined over time. VE was higher and better preserved over time for PHN and HZ-associated hospitalizations than for community HZ.

The role of vitamin C in the treatment of pain: new insights.

The vitamin C deficiency disease scurvy is characterised by musculoskeletal pain and recent epidemiological evidence has indicated an association between suboptimal vitamin C status and spinal pain. Furthermore, accumulating evidence indicates that vitamin C administration can exhibit analgesic properties in some clinical conditions. The prevalence of hypovitaminosis C and vitamin C deficiency is high in various patient groups, such as surgical/trauma, infectious diseases and cancer patients. A number of recent clinical studies have shown that vitamin C administration to patients with chronic regional pain syndrome decreases their symptoms. Acute herpetic and post-herpetic neuralgia is also diminished with high dose vitamin C administration. Furthermore, cancer-related pain is decreased with high dose vitamin C, contributing to enhanced patient quality of life. A number of mechanisms have been proposed for vitamin C's analgesic properties. Herein we propose a novel analgesic mechanism for vitamin C; as a cofactor for the biosynthesis of amidated opioid peptides. It is well established that vitamin C participates in the amidation of peptides, through acting as a cofactor for peptidyl-glycine α-amidating monooxygenase, the only enzyme known to amidate the carboxy terminal residue of neuropeptides and peptide hormones. Support for our proposed mechanism comes from studies which show a decreased requirement for opioid analgesics in surgical and cancer patients administered high dose vitamin C. Overall, vitamin C appears to be a safe and effective adjunctive therapy for acute and chronic pain relief in specific patient groups.