Plasma Vitamin C Concentrations Were Negatively Associated with Tingling, Prickling or Pins and Needles Sensation in Patients with Postherpetic Neuralgia.

Vitamin C deficiency increases the risk of postherpetic neuralgia (PHN). In this cross-sectional study, the relationships among plasma vitamin C concentrations, pain and Leeds assessment of neuropathic symptoms and signs (LANSS) items were investigated during their first pain clinic visit of 120 PHN patients. The factors associated with vitamin C deficiency were determined. Independent predictors of vitamin C deficiency were presented as adjusted odds ratios (AOR) and 95% confidence intervals (CI). The patients had a high prevalence (52.5%) of vitamin C deficiency. Their plasma vitamin C concentrations were negatively associated with spontaneous pain and tingling, prickling or pins and needles sensation according to the LANSS questionnaire. Based on the receiver operator characteristic curve, the cutoffs for plasma vitamin C to predict moderate-to-severe and severe symptoms of sharp sensation were <7.05 and <5.68 mg/L, respectively. By comparison, the patients well-nourished with vitamin C had lower incidences of sharp sensations, sharp pain, and reddish skin. Multivariate analyses revealed that vitamin C deficiency was associated with the low intake of fruit/vegetables (AOR 2.66, 95% CI 1.09-6.48, p = 0.032), peptic ulcer disease (AOR 3.25, 95% CI 1.28-8.28, p = 0.014), and smoking (AOR 3.60, 95% CI 1.33-9.77, p = 0.010). Future studies are needed to substantiate these findings.

Correlation between Galectin-3 and Early Herpes Zoster Neuralgia and Postherpetic Neuralgia: A Retrospective Clinical Observation.

This study aims to explore the value of serum galectin-3 in patients with herpes zoster neuralgia (HZN) and postherpetic neuralgia (PHN) and other factors influencing HZN and PHN occurrence. Samples from forty patients with herpes zoster neuralgia (HZN) (Group H), 40 patients with nonherpes zoster neuralgia (Group N), and 20 cases of health check-up were collected. Patients were divided into PHN group (Group A) and non-PHN group (Group B) according to the occurrence of PHN in Group H. Galectin-3, T-lymphocyte subsets, and IL-6 were recorded in all patients. The changes of galectin-3 in patients with early HZN and PHN were analyzed by single-factor analysis and multifactor analysis. The age (P=0.012) and NRS scores (P < 0.001) of PHN patients were significantly higher than those of non-PHN patients and other neuralgia patients. The ratio of CD3+ (F = 80.336, P < 0.001), CD4+ (F = 12.459, P < 0.001) lymphocyte subsets, and CD4+/CD8+ (F = 15.311, P < 0.001) decreased significantly in PHN patients. The level of blood IL-6 (F = 139.446, P < 0.001) in PHN patients was significantly increased. Serum galectin-3 was significantly higher in HZN patients than in PHN patients (P < 0.05); IL-6 (OR = 10.002, 95% CI: 3.313-30.196, P < 0.001) and galectin-3 (OR = 3.719, 95% CI: 1.261-10.966, P=0.017) were the risk factors for HZN; galectin-3 (OR = 17.646, 95% CI: 2.795-111.428, P=0.002) was also the risk factor for PHN. ROC curve analysis also showed that serum galectin-3 was a better predictor of poor prognosis (AUC = 0.934, P < 0.001). Therefore, as an independent risk factor of HZN and PHN, serum galectin-3 may be used as a new biochemical marker in clinical practice.

Hypovitaminosis Din Postherpetic Neuralgia-High Prevalence and Inverse Association with Pain: A Retrospective Study.

Hypovitaminosis D (25-hydroxyvitamin D (25(OH)D) <75 nmol/L) is associated with neuropathic pain and varicella-zoster virus (VZV) immunity. A two-part retrospective hospital-based study was conducted. Part I (a case-control study): To investigate the prevalence and risk of hypovitaminosis D in postherpetic neuralgia (PHN) patients compared to those in gender/index-month/age-auto matched controls who underwent health examinations. Patients aged ≥50 years were automatically selected by ICD-9 codes for shingle/PHN. Charts were reviewed. Part II (a cross-sectional study): To determine associations between 25(OH)D, VZV IgG/M, pain and items in the DN4 questionnaire at the first pain clinic visit of patients. Independent predictors of PHN were presented as adjusted odds ratios(AOR) and 95% confidence intervals (CI). Prevalence (73.9%) of hypovitaminosis D in 88 patients was high. In conditional logistic regressions, independent predictors for PHN were hypovitaminosis D (AOR3.12, 95% CI1.73-5.61), malignancy (AOR3.21, 95% CI 1.38-7.48) and Helicobacter pylori-related peptic ulcer disease (AOR3.47, 95% CI 1.71-7.03). 25(OH)D was inversely correlated to spontaneous/brush-evoked pain. Spontaneous pain was positively correlated to VZV IgM. Based on the receiver operator characteristic curve, cutoffs for 25(OH)D to predict spontaneous and brush-evoked pain were 67.0 and 169.0 nmol/L, respectively. A prospective, longitudinal study is needed to elucidate the findings.

Clinical Study of Ultrasound-Guided Methylene Blue Thoracic Paravertebral Nerve Block for the Treatment of Postherpetic Neuralgia.

AIM: To investigate the effect of ultrasound-guided methylene blue (MB) thoracic paravertebral nerve block (TPVB) on the treatment of postherpetic neuralgia (PHN). MATERIAL AND METHODS: A total of 27 patients with PHN were treated with ultrasound-guided TPVB. The blocking drug used was an MB compound preparation, and several indexes were recorded, including pain visual analogue scores (VAS), dosage of oral analgesic required, plasma interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and cortisol levels, basic viability, selfassessment, and satisfaction. RESULTS: The patients' VAS after TPVB were significantly reduced when compared to those before blocking. Furthermore, dosage of oral analgesic required, levels of plasma IL-6, TNF-α, and cortisol were reduced, and basic viability and self-assessments were significantly improved (p < 0.05). The treatment method was effective, did not cause any adverse effects, and patients reported higher degrees of satisfaction. CONCLUSION: Ultrasound-guided TPVB exerts significant effects on PHN. The patients' degree of pain and dosage of oral analgesic required were reduced, basic patient viability was improved, and patients reported higher degrees of satisfaction.

Decreased absolute numbers of CD3+ T cells and CD8+ T cells during aging in herpes zoster patients.

Herpes zoster (HZ) is an infectious dermatosis with high incidence worldwide. Age is a key risk factor for HZ, and postherpetic neuralgia (PHN) is the main sequelae. Until now, no index has been available to predict the pathogenesis of PHN, and rare reports have focused on the immune response during aging and PHN. In this study, we selected immunoglobulin and complement proteins as markers for humoral immunity, while T lymphocyte subsets and natural killer (NK) cells were selected as markers for cell immunity, to systematically study the characteristics of immune responses in the peripheral blood of HZ patients. Our data showed that the absolute number of CD3+ T cells and CD8+ T cells decreased during aging and PHN. This implies that more attention should be paid to prevent the occurrence of PHN, especially in the aged population.

Effect of Zhuang medicine medicated thread moxibustion on protomics in serum of postherpetic neuralgia patient with Herpes zoster.

The aim of this study was to observe the effect of Zhuang medicine medicated thread moxibustion on protomics in serum of postherpetic neuralgia patient with herpes zoster and discuss the action mechanism of Zhuang medicine medicated thread moxibustion in treating postherpetic neuralgia (PHN). Patients were divided into three groups in clinic, namely the pre-treatment group (n=20), post-treatment group (n=20) and healthy group (n=20), patients meeting corresponding conditions were recruited in the voluntary principle to accept PHN pain evaluation and protomics tests respectively. Compared with the pre-treatment group, visual analogue scale (VAS) in post-treatment group obviously reduced, protomics indexes like MFG-ES, Lymphotoxin beta/TNFSF3, IL-19, Neuritin, NCAM-1/CD56 and PECAM-1/CD31 obviously changed. The Zhuang medicine medicated thread moxibustion can treat the postherpetic neuralgia patient with herpes zoster, its internal mechanism is to possibly change the protomics indexes like MFG-ES, Lymphotoxin beta/TNFSF3, IL-19, Neuritin, NCAM-1/CD56 and PECAM-1/CD31.

Comparing serum microRNA levels of acute herpes zoster patients with those of postherpetic neuralgia patients.

Postherpetic neuralgia (PHN) is commonly defined as pain persisting for at least 3 months after acute herpes zoster (AHZ) rash presentation. About one-tenth of all acute herpes zoster patients develop PHN. Circulating microRNAs (miRNAs) are promising biomarkers for infectious diseases; however, there has been no relationship established between circulating miRNAs and PHN to date; the aim of the present investigation was to elucidate this relationship.We compared serum levels of miRNA in PHN and AHZ patients. Twenty-nine patients with PHN and 37 patients with AHZ participated. MiRNA serum levels were determined via TaqMan Low Density Array (TLDA) and confirmed individually by RT-qPCR.TLDA results showed that the expression levels of 157 serum miRNAs in PHN patients were distinct from those in AHZ patients. Among these PHN patient serum miRNAs, 17 were upregulated and 139 were downregulated in contrast to those in AHZ patients. Receiver operational characteristic (ROC) curve analysis and RT-qPCR results altogether confirmed that the levels of miR-34c-5p, miR-107, miR-892b, miR-486-3p, and miR-127-5p were notably increased in PHN patients in comparison with those of AHZ patients. These miRNAs in circulation may regulate numerous relevant pathways. A few likely participate in the nervous system and inflammatory reactions.This study is the first to show that the expression profiles of numerous miRNAs vary in the PHN process. Among these, 5 types of serum miRNAs are very likely related to PHN development.

Modulation of serum BDNF levels in postherpetic neuralgia following pulsed radiofrequency of intercostal nerve and pregabalin.

AIM: To study the modulation of serum BDNF levels following integrated multimodal intervention in postherpetic neuralgia (PHN). MATERIALS & METHODS: A randomized, double-blind controlled study was undertaken among patients of thoracic PHN where 30 patients received pregabalin with pulsed radiofrequency and 30 controls received pregabalin with sham treatment. RESULTS: Pain intensity (visual analog scale) was reduced earlier in intervention group (15.3 ± 5.7 at the fourth week) compared with control group (16.3 ± 6.6 at the eighth week). Serum BDNF level increased with time in both the groups with overall increase more pronounced in intervention group. CONCLUSION: Integrated multimodal therapy using minimally invasive pulsed radiofrequency and pregabalin in PHN was effective in early pain reduction with elevated serum BDNF levels.

Anti-cytokine autoantibodies in postherpetic neuralgia.

BACKGROUND: The mechanisms by which varicella zoster virus (VZV) reactivation causes postherpetic neuralgia (PHN), a debilitating chronic pain condition, have not been fully elucidated. Based on previous studies identifying a causative role for anti-cytokine autoantibodies in patients with opportunistic infections, we explored this possibility in PHN. METHODS: Sera from herpes zoster (HZ) patients without and with PHN (N = 115 and 83, respectively) were examined for the presence of autoantibodies against multiple cytokines, and other known autoantigens. In addition, a cohort of patients with complex regional pain syndrome or neuropathic pain was tested for autoantibodies against selected cytokines. Antibody levels against VZV, Epstein Barr virus, and herpes simplex virus-2 were also measured in the HZ and PHN patients. Patient sera with high levels of anti-cytokine autoantibodies were functionally tested for in vitro neutralizing activity. RESULTS: Six PHN subjects demonstrated markedly elevated levels of single, autoantibodies against interferon-α, interferon-γ, GM-CSF, or interleukin-6. In contrast, the HZ and the pain control group showed low or no autoantibodies, respectively, against these four cytokines. Further analysis revealed that one PHN patient with high levels of anti-interleukin-6 autoantibodies had a markedly depressed antibody level to VZV, potentially reflecting poor T cell immunity against VZV. In vitro functional testing revealed that three of the five anti-cytokine autoantibody positive PHN subjects had neutralizing autoantibodies against interferon-α, GM-CSF or interleukin-6. In contrast, none of the HZ patients without PHN had neutralizing autoantibodies. CONCLUSIONS: These results suggest the possibility that sporadic anti-cytokine autoantibodies in some subjects may cause an autoimmune immunodeficiency syndrome leading to uncontrolled VZV reactivation, nerve damage and subsequent PHN.

Local and systemic cytokine expression in patients with postherpetic neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is the painful complication of a varicella zoster virus reactivation. We investigated the systemic and local gene expression of pro- and anti-inflammatory cytokine expression in patients with PHN. METHODS: Thirteen patients with PHN at the torso (Th4-S1) were recruited. Skin punch biopsies were obtained from the painful and the contralateral painless body area for intraepidermal nerve fiber density (IENFD) and cytokine profiling. Additionally, blood was withdrawn for systemic cytokine expression and compared to blood values of healthy controls. We analyzed the gene expression of selected pro- and anti-inflammatory cytokines (tumor necrosis factor-alpha [TNF] and interleukins [IL]-1ß, IL-2, and IL-8). RESULTS: IENFD was lower in affected skin compared to unaffected skin (p<0.05), while local gene expression of pro- and anti-inflammatory cytokines did not differ except for two patients who had 7fold higher IL-6 and 10fold higher IL-10 gene expression in the affected skin compared to the contralateral unaffected skin sample. Also, the systemic expression of cytokines in patients with PHN and in healthy controls was similar. CONCLUSION: While the systemic and local expression of the investigated pro- and anti-inflammatory cytokines was not different from controls, this may have been influenced by study limitations like the low number of patients and different disease durations. Furthermore, other cytokines or pain mediators need to be considered.

[Impacts of bleeding and cupping therapy on serum P substance in patients of postherpetic neuralgia].

OBJECTIVE: To observe the effect of bleeding and cupping therapy on postherpetic neuralgia (PHN) and preliminarily discuss the analgesic mechanism. METHODS: Sixty-four cases of PHN were randomized into two groups, 32 cases in each one. In the bleeding and cupping group, the local pricking with syringe needle and cupping was applied in the local painful area, once every two days. And totally 8 treatments were required. In the pregabalin group, pregabalin was prescribed for oral administration, 150mg/time, twice a day. And totally 16 days of medication were required. Visual analogue scale (VAS) score and the changes of P substance content in the peripheral and local serum before and after treatment were observed in the two groups. METHODS: VAS score and peripheral serum P substance after treatment were lower significantly than those before treatment in the two groups (all P<0.01). The result in the bleeding and cupping group was much more significant (P<0.01). The local serum P substance after treatment was reduced significantly than that before treatment in the bleeding and cupping group [(93.86 +/- 9.87) pg/mL vs (46.13 +/- 6.31) pg/mL, P<0.01]. CONCLUSION: Bleeding and cupping therapy achieves the definite efficacy on PHN and it can reduce significantly peripheral and local serum P substance content in the patients. It is possibly one of the mechanisms of analgesic effect.

Plasma vitamin C is lower in postherpetic neuralgia patients and administration of vitamin C reduces spontaneous pain but not brush-evoked pain.

OBJECTIVES: Plasma vitamin C concentrations have been suggested to be related to pain modulation in postherpetic neuralgia (PHN), an intractable neuropathic pain syndrome. In this study, we first compared plasma concentrations of vitamin C between healthy volunteers and PHN patients and then designed a symptom-based and mechanism-based approach to assess the analgesic effect of intravenous vitamin C on spontaneous and brush-evoked pain. METHODS: Study 1 was cross-sectional that enrolled 39 healthy volunteers and 38 PHN patients. Study 2 was a double-blinded, placebo-controlled intervention study, which comprised 41 patients randomly allocated into the ascorbate group and placebo. Each patient received normal saline infusion with or without ascorbate on days 1, 3, and 5 and answered questionnaires that included side effects; numeric rating pain scale (NRS) on spontaneous and brush-evoked pain on days 1, 3, 5, and 7; and patient global impression of change on spontaneous and brush-evoked pain on day 7. RESULTS: Study 1 revealed that plasma concentrations of vitamin C were significantly lower in patients with PHN than in healthy volunteers (P<0.001). Study 2 showed that ascorbate treatment effectively restored plasma vitamin C concentrations in the patients and decreased spontaneous pain by 3.1 in NRS from baseline to day 7, as compared with a decrease of 0.85 in NRS by placebo treatment (P<0.001). Conversely, ascorbate treatment did not significantly affect brush-evoked pain. Ascorbate treatment also resulted in a better efficacy than placebo in patient global impression of change on spontaneous pain (P<0.001) on day 7 and did not affect brush-evoked pain. No side effects were observed. CONCLUSIONS: Plasma vitamin C status plays a role in PHN, and intravenous ascorbate helps relieve spontaneous pain in PHN.