Postherpetic Neuralgia Research Articles

Immune cells mediate the effects of gut microbiota on neuropathic pain: a Mendelian randomization study.

The gut microbiota may be involved in neuropathic pain. However, the causal association between gut microbiota and neuropathic pain remains unclear. Whether immune cells and inflammatory factors mediate the pathway from gut microbiota to neuropathic pain has not been elucidated. We obtained the summary data of 412 gut microbiota, 731 immune cells, 91 inflammatory factors, and five types of neuropathic pain (drug-induced neuropathy, postherpetic neuralgia, sciatica, trigeminal neuralgia, and unspecified neuralgia) from large-scale genome-wide association study (GWAS) datasets and the FinnGen database. We used bidirectional Mendelian randomization (MR) analysis to explore the causal association between gut microbiota and neuropathic pain. Additionally, we conducted a mediation analysis to identify whether immune cells and inflammatory factors act as mediators within these causal relationships. Our study revealed 30 causal relationships between 26 gut bacterial taxa and five types of neuropathic pain, including four associated with drug-induced neuropathy, six with postherpetic neuralgia, five with sciatica, eight with trigeminal neuralgia, and seven with unspecified neuralgia. Moreover, we identified 35 gut bacterial pathway abundances causally involved in neuropathic pain. The reverse MR analysis showed no evidence of reverse causality from gut microbiota to neuropathic pain. Mediation analysis demonstrated that the immune cell phenotype "HLA-DR++ monocyte % leukocyte" mediated the causal relationship between p_Proteobacteria and sciatica with a mediation proportion of 36.15% (P = 0.038), whereas "CD11c on CD62L+ myeloid dendritic cell" mediated the causal pathway from assimilatory sulfate reduction to trigeminal neuralgia with a mediation proportion of 27.90% (P = 0.041). This study identified the causal relationships between several specific gut microbiota and various neuropathic pain subtypes. Additionally, two immune cells may act as potential mediators in the pathways from gut microbiota to neuropathic pain.

Clinical profile of herpes zoster-related hospitalizations and complications: A French population-based database study

To estimate the incidence of hospitalization with a diagnosis of herpes zoster (HZ) and post-herpetic neuralgia (PHN) in France between 2013 and 2020, overall and stratified by age-group and immune status. Retrospective observational, database study, using the French hospital discharge database, which includes private and public data for all day-care and inpatient stays. Adults aged ≥18 years, hospitalized between January 1, 2013, and December 31, 2020, with a diagnosis of HZ or PHN were included. Overall, 62 077 adults had a first hospitalization with a diagnosis of HZ or PHN during the observation period. HZ and/or PHN incidence ranged between 14.6 and 16.3 hospitalizations/100 000 persons and was highest in people aged ≥80 years (97.6 hospitalizations/100 000 persons). The immunocompromised (IC) population accounted for 22% of the overall study population. IC patients had longer lengths of stay for HZ per episode compared with non-IC patients (15.5 ± 19.4 days vs 12.2 ± 13.5 days) and higher in-patient mortality (8% vs 4%). Average annual hospitalization costs per patient were higher in the IC vs non-IC population (€8018 vs €5603). Older age increases hospitalization rates up to 6-fold and IC status increases in-patient mortality up to two-fold.

VZV Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation in Children: When to Stop?

Acyclovir treatment is an efficient prophylaxis to prevent varicella-zoster virus (VZV) reactivation after allogeneic hematopoietic stem cell transplantation (HSCT). This single center retrospective study tried to determine if the lymphocytes immunophenotyping could help to determine the duration of prophylaxis, and evaluated complications, and associated risk factors for VZV infection. Eighty-four children underwent an allogeneic HSCT, in which 77 received an acyclovir prophylaxis. Twenty-one of the 77 had a VZV infection with an incidence rate of 1.30 per 100 patients-months (exact 95% CI, 0.81 to 2.01). Among these 21 patients with VZV infection, 16 had an infection after withdrawing acyclovir prophylaxis within a median of 49 days (range, 11 days-5.8 months). Thirty-five percent of the VZV infected patients were hospitalized, 9% had a visceral dissemination, and 9% had postherpetic neuralgia. In multivariate analysis, higher VZV infection rate was associated with conditioning regimen with total body irradiation, immunoglobulin substitution, and antithymocyte globulin. The incidence of VZV infection increased significantly when patients had a CD4+ lymphocytes count below 23% (cHR 3.28 [95% CI, 1.09-9.81]; p = 0.03) or a CD4+/CD8+ ratio less than 0.9 (cHR 3.13 [95% CI, 1.04-9.36]; p = 0.04) at the time of stopping acyclovir prophylaxis. After cessation of acyclovir prophylaxis, VZV reactivation can occur and be responsible for morbidity after allogeneic HSCT. This study suggests that the proportion of CD4+ lymphocytes and the CD4+/CD8+ ratio can inform decisions about the duration of acyclovir prophylaxis after allogeneic HSCT to prevent VZV reactivation.

Making Sense of Topical Pain Relief Options: Comparing Topical Analgesics in Efficacy and Safety.

In patients with musculoskeletal (MSK) conditions, pain is the leading contributor to disability and significantly limits mobility and dexterity. This narrative review describes the efficacy and safety of topical analgesics in common use today. Secondary literature gained via a literature search using PubMed.gov and the Cochrane library were used. Recent literature (2000-2023) on several major classes of topical analgesics and topical delivery systems were reviewed to provide strength of recommendation taxonomy (SORT) levels. A total of 86 articles were reviewed. Level 2. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) and cabbage leaf wraps (CLW) appear to be best suited for multiple types of acute MSK pain, and topical nitroglycerin is helpful when used specifically for rotator cuff pain in patients seeking relief while performing activities of daily living and willing to treat for long periods of time. For compounded topical formulations, it may be better to offer single agent creams based on patient preferences. Little data support the use of cryotherapy. Traumeel could be a promising natural analgesic that compares with diclofenac. Topical lidocaine appears best suited for postherpetic neuropathic pain. O24 is a reasonable alternative with a low risk profile to treat pain in patients with fibromyalgia syndrome. Choice of topical agents should be guided by current evidence accounting for type of pain, medication side effects, patient comorbidities, as well as patient preference, convenience, and cost. Of the topical analgesics and modalities reviewed, SORT level A evidence was found for topical NSAID use in decreasing MSK pain, topical lidocaine for postherpetic neuralgia, and nitroglycerin patches for treating rotator cuff pain if used for prolonged periods of time. Alternative treatments such as CLW and Traumeel show promising results (SORT level B).

Causal effect of gut microbiota on occurrence of herpes zoster and postherpetic neuralgia, and role of Tyzzerella 3

BackgroundPrevious research has established connections between gut microbiota, immune modulation, and several virus-related diseases. However, no study has explored the relationships between gut microbiota and herpes zoster and postherpetic neuralgia (PHN).MethodsA total of 205 taxa of gut microbiota were regarded as exposures. The occurrences of herpes zoster and PHN were selected as outcomes. The causal effects of gut microbiota on herpes zoster and PHN were estimated with multiple methods for two-sample Mendelian randomization, such as inverse variance weighted (IVW), MR–Egger, and weighted median. All results were subjected to FDR correction to prevent from possibility of multiple comparison.ResultsAmong the significant findings, four taxa and one genus were identified as facilitators of herpes zoster and PHN, respectively. Conversely, six genera and eleven taxa were found to inhibit herpes zoster and PHN, respectively. The causal effect of the Tyzzerella 3 was confirmed through FDR correction, making it a key focus in this study. Specifically, it was found to causally facilitate herpes zoster primarily with IVW (OR 1.420, 95% CI 1.174–1.718, p < 0.001, q = 0.039), as there is no heterogeneity or horizontal pleiotropy found.ConclusionsWith investigation of the causal association between gut microbiota, and herpes zoster/PHN, significant findings were identified in 22 different taxa. Among them, Tyzzerella 3 keeps significant after multiple comparison correction, and displays potential to facilitate the occurrence of herpes zoster.Graphical

Vaccinations in pulmonary diseases - part 2: herpes zoste, RSV, pneumococcal infection and pertussis

RSV is a common cause of respiratory tract infections, posing a risk of severe disease, particularly for newborns and infants, as well as in older individuals with pre-existing conditions. Two safe and effective RSV vaccines were approved in 2023. These vaccines elicit protective antibodies and offer robust protection with no additional benefit from annual boosters. Both vaccines have been approved for individuals aged 60 years and older, while one of the vaccines has also been approved in pregnant women to elicit maternal immunity for passive protection of the unborn child. In Germany, RSV vaccination is currently recommended for all individuals aged 75 years and older, as well as people aged 60-74 years of age with severe underlying conditions. PNEUMOCOCCAL INFECTION: Streptococcus pneumoniae is a primary cause of community-acquired pneumonia (CAP). Since early 2022, a 20-valent conjugate vaccine (PCV20) is approved and recommended for people over 60 years of age and individuals over 18 years of age with risk factors. PCV20 replaces the 23-valent polysaccharide vaccine (PPV23) previously recommended for those over 60 years of age. Although viewed primarily as a childhood disease, the majority of infections affect adults. Patients with chronic respiratory diseases are at a higher risk for severe clinical course of pertussis infection. It has therefore been recommended that all adults should get a pertussis booster with their next scheduled tetanus vaccination, given as a combination vaccine (Tdap). For risk groups (healthcare personnel, community facilities) a booster vaccination every 10 years is recommended. Herpes Zoster (shingles) is caused by the varicella-zoster virus, and reactivations can lead to painful skin lesions and potential complications such as herpes zoster oticus, meningitis, or postherpetic neuralgia. People with chronic lung diseases such as COPD or asthma are at increased risk of herpes zoster-related complications. A recombinant adjuvanted inactivated vaccine was approved in 2018 and offers robust protection against herpes zoster and its complications. The vaccine is recommended for all people over 60 years of age and for certain risk groups over 50 years of age.

A central and peripheral dual neuromodulation strategy in pain management of zoster-associated pain.

Spinal cord stimulation (SCS) has shown effectiveness in relieving zoster-associated pain (ZAP), but some patients still experience moderate or severe pain after SCS treatment. This study aims to evaluate the impact of SCS combined with dorsal root ganglion (DRG) pulsed radiofrequency (PRF) as a dual neuromodulation strategy on the prognosis of ZAP. The clinical records of patients diagnosed with ZAP who underwent SCS (SCS group) or SCS combined with PRF (SCS + PRF group) at The Third Xiangya Hospital, Central South University, were retrospectively analyzed to compare the effectiveness of the two treatment approaches for ZAP. Outcome measures included changes in Visual Analog Scale (VAS) scores before and after neuromodulation treatment, response rates, and incidence of progression to postherpetic neuralgia (PHN).13 SCS patients and 15 SCS + PRF patients were analyzed. Admission VAS scores were similar (P = 0.934). Upon discharge, no significant differences in VAS or response rates were observed (P > 0.05). However, at 6-month follow-up, the SCS + PRF group had lower VAS scores (1.53 ± 1.06 vs. 3.23 ± 1.50, P < 0.001) and a lower proportion of residual moderate pain (P = 0.041). None in the SCS + PRF group progressed to PHN in the acute/subacute phases, differing significantly from the SCS group (P = 0.038).Therefore, SCS combined with DRG PRF is feasible and effective in the treatment of ZAP. This dual neuromodulation strategy may be a more appropriate regimen for the treatment of ZAP.

The risk of postherpetic neuralgia in COVID-19 vaccination-associated herpes zoster: A retrospective cohort study using TriNetX

BackgroundThe administration of the COVID-19 vaccine has been linked to the development of herpes zoster (HZ). However, studies examining the clinical outcomes in COVID-19 vaccination-associated and non-COVID-19 vaccination-associated HZ are lacking. ObjectiveTo investigate the risk of postherpetic neuralgia in COVID-19 vaccination associated HZ. MethodsA total of 7200 patients with COVID-19 vaccination-associated HZ and 7200 matched controls were enrolled from the US Collaborative Network in the TriNetX database. The main outcome of this study was the development of PHN.Patients were followed-up from 3 months after HZ until PHN diagnoses, withdrawal from the database, or October 8, 2024. ResultsWe observed that patients with COVID-19 vaccination-associated HZ had a significantly higher risk of developing PHN as compared to the control group, with hazard ratio of 1.69 (> 3 months), 1.80 (> 6 months), 1.86 (> 1 year), and 1.93 (>2 years), respectively. Additionally, the association remained significant in the stratified analysis, which included sex, age, malignancy status, and initial use of antiviral agents. ConclusionThis study showed that COVID-19 vaccination-associated HZ demonstrated a significantly higher risk of developing PHN.

Relieving postherpetic neuralgia pain via gabapentin-loaded bigels as an auspicious topical drug delivery system.

Over the past decades, a substantial portion of the population worldwide has been infected with varicella zoster and most cases developed shingles. Unfortunately, shingles is usually accompanied by postherpetic neuralgia, which may persist for months to years after the resolution of the viral infection. Gabapentin is an orallygamma-aminobutyric acid analogue approved by the Food and Drug Administration to manage shingles postherpetic neuralgia. However, gabapentin shows nonlinear pharmacokinetics, with variable absorption and bioavailability along with its short half-life and long side effects that may include dizziness and somnolence, which calls for an appropriate topical dosage form. Bigels are unique semisolid dosage forms with boosted penetrability and satisfactory hydrophilic texture. The current work pointed to formulating gabapentin-loaded bigels for the treatment of postherpetic neuralgia, where the analysis and optimization of design were performed via Design-Expert®. The selected bigel (F5), incorporating 400mg Span 60, 1000mg Tween 80, and 1000mg Transcutol, displayed spherical nanosized particles with acceptable viscosity and spreadability. Subsequent topical application of the selected bigel on the skin of Wistar rats, F5, demonstrated a boosted accumulation of gabapentin in the skin similar to PLO gel but superior to the drug solution. Furthermore, a histopathological study demonstrated the biosafety of the selected bigel when applied topically. Accordingly, gabapentin-loaded bigel would be considered a potentially topical dosage form for the delivery of gabapentin for the management of postherpetic neuralgia.

Possible Role of Platelet-Rich Plasma in the Treatment of Patients with Postherpetic Neuralgia: A Prospective, Single-Arm, Open-Label Clinical Study

Abstract Background: Currently, no treatment can fully and finally treat postherpetic neuralgia (PHN). Objectives: This study aimed to evaluate the possible efficacy of autologous intralesional platelet-rich plasma (PRP) injection in treating patients with PHN. Materials and Methods: A prospective, single-arm, open-label clinical study was conducted on 45 patients with PHN attending the Dermatology Outpatient Clinics of Sohag University Hospital, Egypt, between November 2019 and November 2021. Patients were subjected to full clinical general and dermatologic examinations. Patient’s assessment included; severity of pain through visual analogue scale (VAS), numerical rating scale (NRS), and verbal rating scale (VRS), in addition to Medical Outcomes Study 36 Item Short-Form (SF-36). Patients were treated by autologous PRP injection every 2 weeks for 2 months (4 sessions). Patients were evaluated before every session and 3- months after the last session. Results: There was a significantly decreased VAS, NRS, VRS, and SF-36 questionnaire values in the last session and three months after the last session. There was a highly significant moderate correlation between both scales (VAS and VRS) and patient’s age in years and who have aggravating factors. Likewise, there was a significant moderate positive correlation between scales (VAS and VRS) and the disease duration, medical co-morbidities, and associated myalgia. Limitations: These findings require further confirmations on more inclusive large-sized multicenter, randomized, placebo-controlled, clinical trials with longer follow-up. Conclusion: This clinical pilot study concluded that autologous intralesional PRP injection was an effective therapeutic option for patients with PHN.

8. Herpes zoster and post herpetic neuralgia.

Patients suffering from postherpetic neuralgia (PHN) report unilateral chronic pain in one or more dermatomes after an acute herpes zoster (HZ) infection. The incidence of acute HZ ranges between three and five patients per 1000 person-years. In one out of four patients, acute HZ-related pain will transition into PHN. PHN can be very disabling for patients and reduce quality of life. Additionally, the treatment of PHN is characterized by high failure rates. The aim of this review is to give an update on the previous practical guideline published in 2011 and revised in 2015 (published in 2019) and to provide an overview of current interventional treatment options for HZ infection and PHN. The literature on the diagnosis and treatment of HZ and PHN was systematically reviewed and summarized. The most important treatment for acute HZ-related pain is antiviral therapy within 72 h of symptom onset. Additional symptomatic treatment options are analgesic drugs according to the WHO pain ladder, tricyclic antidepressants (eg, nortriptyline), and antiepileptic drugs (eg, gabapentin). If pain is not sufficiently reduced, interventional treatment such as an epidural injection with local anesthetics and corticosteroids or pulsed radiofrequency of the dorsal root ganglion (DRG) are options. Treatment for PHN is preferably transdermal capsaicin, lidocaine, or oral drugs such as antidepressants or antiepileptics. Treatment of acute HZ-related pain especially PHN is challenging. Besides the conventional treatment for PHN, interventional management is considered a new treatment option. PRF of DRG seems to be the most promising interventional management.

Assessment of ultrasound-guided intercostal nerve block for acute herpes zoster and its' possible prophylaxis for postherpetic neuralgia: a retrospective and case-controlled trial.

This study aimed to compare the intercostal nerve block (ICNB) and thoracic paravertebral block (TPVB) for acute herpes zoster-associated pain (ZAP) and possible prophylaxis for post-herpetic neuralgia (PHN). This study enrolled 128 patients with ZAP. Their records were stratified into standard antiviral treatment (AVT) plus US-guided TPVB (the TPVB group), AVT plus US-guided ICNB (the ICNB group) or AVT alone (the control group). Herpes zoster (HZ)-related burden of illness (HZ-BOI) within the post-procedural 30 days was defined as the primary endpoint, determined by a composite of pain severity and follow-up duration. Procedure time, rescue analgesic requirement, PHN incidence, health-related quality of life and side effects were also recorded. Significantly lower HZ-BOI-AUC30 was reported in the TPVB and ICNB groups as compared to the control group, with a mean difference of 57.5 (P < 0.001) and 40.3 (P = 0.003), respectively. However, there was no difference between the TPVB and ICNB groups (P = 0.978). Both TPVB and ICNB reported significantly greater improvements in PHN incidence, EQ-5D-3L scores and rescue analgesic requirements during follow-up, as opposed to the control AVT. Shorter procedure time was observed in ICNB as compared to TPVB (16.47 ± 3.39 vs. 11.69 ± 2.58, P < 0.001). Both US-guided TPVBs and ICNBs were effective for ZAP, and accounted for possible prophylaxis for PHN, as compared to AVT alone. The ICNB approach could be recommended as an alternative to conventional TPVB with a better consumed procedure time and side effect profile.a.

Identifying and Evaluating Biological Markers of Postherpetic Neuralgia: A Comprehensive Review.

Postherpetic neuralgia (PHN) manifests as persistent chronic pain that emerges after a herpes zoster outbreak and greatly diminishes quality of life. Unfortunately, its treatment efficacy has remained elusive, with many therapeutic efforts yielding less than satisfactory results. The research to discern risk factors predicting the onset, trajectory, and prognosis of PHN has been extensive. However, these risk factors often present as nonspecific and diverse, indicating the need for more reliable, measurable, and objective detection methods. The exploration of potential biological markers, including hematological indices, pathological insights, and supportive tests, is increasing. This review highlights potential biomarkers that are instrumental for the diagnosis, management, and prognosis of PHN while also delving deeper into its genesis. Drawing from prior research, aspects such as immune responsiveness, neuronal injury, genetic makeup, cellular metabolism, and pain signal modulation have emerged as prospective biomarkers. The immune spectrum spans various cell subtypes, with an emphasis on T cells, interferons, interleukins, and other related cytokines. Studies on nerve injury are directed toward pain-related proteins and the density and health of epidermal nerve fibers. On the genetic and metabolic fronts, the focus lies in the detection of predisposition genes, atypical protein manifestations, and energy-processing dynamics, with a keen interest in vitamin metabolism. Tools such as functional magnetic resonance imaging, electromyography, and infrared imaging have come to the forefront in the pain signaling domain. This review compiles the evidence, potential clinical implications, and challenges associated with these promising biomarkers, paving the way for innovative strategies for predicting, diagnosing, and addressing PHN.

Predictive Value of Current Perception Threshold for Prognosis of Pulsed Radiofrequency in Patients with Acute Herpetic Neuralgia.

This study aimed to evaluate the prognostic accuracy of the Current Perception Threshold (CPT) in Acute Herpetic Neuralgia (AHN) patients receiving Pulsed Radiofrequency (PRF) therapy and to develop a corresponding prognostic model. We retrospectively analyzed data from 106 AHN patients treated with PRF between January 2022 and May 2023. The occurrence of Postherpetic Neuralgia (PHN) after treatment categorized patients into non-PHN and PHN groups. The predictive role of CPT indices for PRF outcomes was assessed using the Receiver Operating Characteristic (ROC) curve and Area Under Curve (AUC). Then the dataset was split into a training set (n=74) and a validation set (n=32). Factors associated with PHN development were identified using univariate and multivariate logistic regression. A nomogram model was developed using significant predictors and internal validation was performed using valid set data. Among the 106 patients, 45had a poor prognosis. Significant differences in age, preoperative Numerical Rating Scale (NRS) score, and 5Hz CPT ratio were observed between the groups (p<0.05). Logistic regression identified these factors as independent predictors for PRF prognosis (p<0.05). The 5Hz CPT ratio demonstrated predictive value (AUC= 0.764, 95% CI: 0.674-0.855). The nomogram model, incorporating these predictors, showed high AUC in both the training (0.863, 95% CI: 0.776-0.950) and validation sets (0.859, 95% CI: 0.721-0.998). Calibration curves indicated good model fit, and the Hosmer-Lemeshow test confirmed this (p>0.05). Decision Curve Analysis (DCA) highlighted the model's predictive advantage. The 5Hz CPT ratio can predict the prognosis of PRF in AHN patients. The nomogram model has high precision and clinical utility. It can help identify AHN patients with a poor PRF prognosis at an early stage and assist in clinical decision-making.

Opioids and Cannabinoids in Neurology Practice.

Opioid and cannabinoid therapies for chronic pain conditions including neuropathic pain are controversial. Understanding patient and prescribing factors contributing to risks and implementing risk mitigation strategies optimizes outcomes. The ongoing transformation from a biomedical model of pain care toward a biopsychosocial model has been accompanied by a shift away from opioid therapy for pain, in particular for chronic pain. Opioid overdose deaths and opioid use disorder have greatly increased in the last several decades, initially because of increases in opioid prescribing and more recently associated with illicit drug use, in particular fentanyl derivatives. Opioid risk mitigation strategies may reduce risks related to opioid prescribing and tapering or discontinuation. Opioid therapy guidelines from the Centers for Disease Control and Prevention have become the consensus best practice for opioid therapy. Regulatory agencies and licensing medical boards have implemented restrictions and other mandates regarding opioid therapy. Meanwhile, interest in and use of cannabinoids for chronic pain has grown in the United States. Opioid therapy is generally not recommended for the chronic treatment of neuropathic pain conditions. Opioids may be considered for temporary use in patients with severe pain related to selected neuropathic pain conditions (such as postherpetic neuralgia), and only as part of a multimodal treatment regimen. Opioid risk mitigation strategies include careful patient selection and evaluation, patient education and informed consent, querying the state prescription drug monitoring programs, urine drug testing, and issuance of naloxone as potential rescue medication. Close follow-up when initiating or adjusting opioid therapy and frequent reevaluation during long-term opioid therapy is required. There is evidence for the efficacy of cannabinoids for neuropathic pain, with meaningful response rates in select patient populations.

Design and in vitro/in vivo evaluation of chitosan-polyvinyl alcohol copolymer material cross-linked by dynamic borate ester covalent for pregabalin film-forming delivery system

This research introduced a novel polymer synthesized by combining chitosan and modified polyvinyl alcohol, cross-linked with boric acid using dynamic covalent bonds. The polymer was developed to formulate a pregabalin Film-forming system (FFS) for treating postherpetic neuralgia via topical application, showcasing notable skin adhesion and drug delivery properites. The chitosan-boric acid-modified polyvinyl alcohol polymer was analyzed using NMR, FTIR. The exceptional features of the optimized FFS were evaluated through rheometer, Differential scanning calorimetry (Tg = 45.98 °C), contact angle (θ = 78.62°). The elongation (60.05 ± 3.67 %), cohesion (56.94 ± 4.65 MPa) and skin adhesion (58.12 ± 2.99 kPa) of chitosan-boric acid-modified polyvinyl alcohol were found to be 5.2, 6.8, and 8.3 times higher than those of the pure chitosan film, attributed to the double network structure formed by the cross-linked reversible dynamic covalent bond. The optimized pregabalin FFS exhibited increased in vitro (86.25 ± 1.87 μg/g) and in vivo (100.42 ± 7.44 μg/g) skin retention amounts compared to in vivo oral administration (28.43 ± 4.61 μg/g). In summary, the utilization of borate ester dynamic covalent bonds in developing chitosan-based film-forming polymer proved beneficial in improving skin adhesion and topical therapeutic effectiveness, thereby mitigating the risk of systemic side effects associated with oral administration.

Peripheral Nerve Stimulation for Neuropathic Pain Management: A Narrative Review.

This narrative review examines the therapeutic efficacy of peripheral nerve stimulation (PNS) in the treatment of neuropathic pain (NP), a type of pain arising from lesions or diseases of the somatosensory system with a global prevalence ranging from 6.90% to 10.00%. Traditional pharmacological interventions often fall short for many persons, highlighting the need for alternative treatments such as PNS, which has demonstrated significant promise with minimal side effects. The review summarizes the effectiveness of PNS in various NP conditions, including trigeminal neuralgia and postherpetic neuralgia, and underscores the need for further research to refine treatment approaches. The mechanism of PNS is discussed, involving the activation of non-nociceptive Aβ fibers and modulation of neurotransmitters, and offering pain relief through both peripheral and central pathways. Despite the proven efficacy of PNS, challenges remain, including the need for randomized controlled trials and the optimization of stimulation parameters. The review concludes that PNS is a promising treatment modality for NP, warranting additional high-quality trials to solidify its role in clinical practice.

Causal links between blood inflammation markers and postherpetic neuralgia risk: insights from a two-sample Mendelian randomization study.

Previous studies have suggested an association between blood inflammation-related factors and postherpetic neuralgia. However, the causal relationship between blood inflammation-related factors and postherpetic neuralgia remains unclear. We employed a bidirectional Two-sample Mendelian randomization (MR) analysis to explore the causal relationship between blood inflammation-related factors and postherpetic neuralgia. The instrumental variables were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. The instrumental variables of the blood inflammation-related factors come from the database numbers GCST004420 to GCST004460 and GCST90029070. Postherpetic neuralgia has 195,191 samples with a total of 16,380,406 single nucleotide polymorphisms (SNPs). MR analyses were performed using inverse-variance weighted, MR-Egger, and weighted median methods. The MR results revealed a significant causal effect of Macrophage Inflammatory Protein 1 Beta (MIP1β) on reducing the risk of postherpetic neuralgia (95%CI = 0.492-0.991, p = 0.044). Additionally, higher levels of interleukin (IL)-10 (95%CI = 0.973-0.998, p = 0.019) and IL-12p70 (95%CI = 0.973-0.997, p = 0.013) were associated with a lower risk of postherpetic neuralgia. Other inflammatory markers showed no significant causal relationship with this condition. This study identifies MIP1β, IL-10, and IL-12p70 as potential therapeutic targets for preventing or treating postherpetic neuralgia, underscoring the need for further research in this area.

Glycoprotein E-Displaying Nanoparticles Induce Robust Neutralizing Antibodies and T-Cell Response against Varicella Zoster Virus.

The Varicella zoster virus (VZV), responsible for both varicella (chickenpox) and herpes zoster (shingles), presents significant global health challenges. While primary VZV infection primarily affects children, leading to chickenpox, reactivation in later life can result in herpes zoster and associated post-herpetic neuralgia, among other complications. Vaccination remains the most effective strategy for VZV prevention, with current vaccines largely based on the attenuated vOka strains. Although these vaccines are generally effective, they can induce varicella-like rashes and have sparked concerns regarding cell virulence. As a safer alternative, subunit vaccines circumvent these issues. In this study, we developed a nanoparticle-based vaccine displaying the glycoprotein E (gE) on ferritin particles using the SpyCatcher/SpyTag system, termed FR-gE. This FR-gE nanoparticle antigen elicited substantial gE-specific binding and VZV-neutralizing antibody responses in BALB/c and C57BL/6 mice-responses that were up to 3.2-fold greater than those elicited by the subunit gE while formulated with FH002C, aluminum hydroxide, or a liposome-based XUA01 adjuvant. Antibody subclass analysis revealed that FR-gE produced comparable levels of IgG1 and significantly higher levels of IgG2a compared to subunit gE, indicating a Th1-biased immune response. Notably, XUA01-adjuvanted FR-gE induced a significant increase in neutralizing antibody response compared to the live attenuated varicella vaccine and recombinant vaccine, Shingrix. Furthermore, ELISPOT assays demonstrated that immunization with FR-gE/XUA01 generated IFN-γ and IL-2 levels comparable to those induced by Shingrix. These findings underscore the potential of FR-gE as a promising immunogen for the development of varicella and herpes zoster vaccines.

Natural Language Processing Versus Diagnosis Code-Based Methods for Postherpetic Neuralgia Identification: Algorithm Development and Validation.

Diagnosis codes and prescription data are used in algorithms to identify postherpetic neuralgia (PHN), a debilitating complication of herpes zoster (HZ). Because of the questionable accuracy of codes and prescription data, manual chart review is sometimes used to identify PHN in electronic health records (EHRs), which can be costly and time-consuming. This study aims to develop and validate a natural language processing (NLP) algorithm for automatically identifying PHN from unstructured EHR data and to compare its performance with that of code-based methods. This retrospective study used EHR data from Kaiser Permanente Southern California, a large integrated health care system that serves over 4.8 million members. The source population included members aged ≥50 years who received an incident HZ diagnosis and accompanying antiviral prescription between 2018 and 2020 and had ≥1 encounter within 90-180 days of the incident HZ diagnosis. The study team manually reviewed the EHR and identified PHN cases. For NLP development and validation, 500 and 800 random samples from the source population were selected, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), F-score, and Matthews correlation coefficient (MCC) of NLP and the code-based methods were evaluated using chart-reviewed results as the reference standard. The NLP algorithm identified PHN cases with a 90.9% sensitivity, 98.5% specificity, 82% PPV, and 99.3% NPV. The composite scores of the NLP algorithm were 0.89 (F-score) and 0.85 (MCC). The prevalences of PHN in the validation data were 6.9% (reference standard), 7.6% (NLP), and 5.4%-13.1% (code-based). The code-based methods achieved a 52.7%-61.8% sensitivity, 89.8%-98.4% specificity, 27.6%-72.1% PPV, and 96.3%-97.1% NPV. The F-scores and MCCs ranged between 0.45 and 0.59 and between 0.32 and 0.61, respectively. The automated NLP-based approach identified PHN cases from the EHR with good accuracy. This method could be useful in population-based PHN research.