Postherpetic Neuralgia Patients Research Articles

Effect of AMPK Subunit Alpha 2 Polymorphisms on Postherpetic Pain Susceptibility in Southwestern Han Chinese.

IntroductionAdenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) can influence energy metabolism. Energy metabolism imbalance is closely associated with the occurrence of neuropathic pain (NeP). Rs10789038 and rs2796498 are genetic polymorphisms of PRKAA2, the gene encoding AMPK, which is closely related to energy metabolism imbalance. This study aimed to explore the relationship between PRKAA2 and postherpetic neuralgia (PHN) in the southwestern Chinese Han population.MethodsThis study enrolled 132 PHN patients and 118 healthy subjects. The rs10789038 and rs2796498 PRKAA2 genotypes were identified in all participants. The association between these single nucleotide polymorphisms and PHN susceptibility was evaluated in the dominant and recessive models. Haplotype analysis of patients with PHN and healthy controls was performed.ResultsThe PHN patients were older than the healthy subjects (P < 0.05); however, the other clinical characteristics between two groups were not significantly different (all P >0.05). Genotypes and allele frequencies differed significantly between PHN patients and healthy subjects in the rs10789038 polymorphism (P < 0.05), but not in rs2796498 (P > 0.05). In addition, the GG haplotype of rs10789038-rs2796498 correlated negatively with PHN occurrence in haplotype analysis (P < 0.05).ConclusionPHN occurrence may be related to the PRKAA2 rs10789038 A>G genetic polymorphism in the southwestern Chinese Han population.

The relative frequency of pruritus in postherpetic neuralgia patients presenting to the pain clinic and associative factors.

Postherpetic neuralgia (PHN) is the most common complication of herpes zoster, whereas postherpetic pruritus (PHP) a rare one. Although PHN has been extensively studied, few studies have investigated PHP. The purpose of this study was to investigate PHP incidence and associated factors in patients with PHN. This was a retrospective study of patients with PHN. A total of 645 patients were included. This study conducted in a single university hospital. Data included age, sex, height, weight, pain score, PHN site, medications, nerve blocks, and pulsed radiofrequency treatment. Data also included PHP onset and duration among those with PHP. We divided patients into 2 groups: the control group (group C), comprising those without PHP, and pruritus group (group P), comprising those with PHP. The correlation of PHP with other factors was analyzed. Of 207 patients, 58 were in group P whereas 149 in group C. The mean onset time and duration of PHP were 96.5 and 278.6 days, respectively. Pain scores were lower in group P than in group C after 3 and 4 months following vesicle formation. Patients with PHN in the trigeminal nerve had a higher incidence of PHP compared to those with PHN in others. Twenty-eight percent of patients with PHN developed PHP. At 3 and 4 months after vesicle formation, patients with PHP had greater pain improvement compared to those without. Patients with PHN in the trigeminal nerve also had a higher incidence of PHP compared to others.

Resting-State Functional Connectivity Analyses: Brain Functional Reorganization in a Rat Model of Postherpetic Neuralgia.

Postherpetic neuralgia (PHN) is a chronic neuropathic pain syndrome, similar to other chronic pains, the mechanisms of which are not fully understood. To further understand the neural mechanism of this chronic pain and its transition, we performed functional magnetic resonance imaging (fMRI) scans on PHN rat models. Twelve PHN rat models were established by intraperitoneal injection of resiniferatoxin, with an additional 12 rats serving as controls. Nociceptive behavioral tests were performed on these rats and fMRI scans were performed on days 7 and 14 after modeling. Functional connection (FC) analysis was used to investigate the brain FC alterations associated with chronic pain in PHN rats, with the anterior cingulate cortex (ACC) as a seed. Nociceptive behavioral tests showed that PHN rats presented symptoms similar to those of PHN patients. FC analysis showed that compared to the control group, the PHN group showed different FC patterns on days 7 and 14. As can be seen, the brain FC alterations in the rat model of PHN changed dynamically, shifting from brain regions processing sensory information to regions processing emotions and motives.

Pain-related reorganization in the primary somatosensory cortex of patients with postherpetic neuralgia.

Studies on functional and structural changes in the primary somatosensory cortex (S1) have provided important insights into neural mechanisms underlying several chronic pain conditions. However, the role of S1 plasticity in postherpetic neuralgia (PHN) remains elusive. Combining psychophysics and magnetic resonance imaging (MRI), we investigated whether pain in PHN patients is linked to S1 reorganization as compared with healthy controls. Results from voxel-based morphometry showed no structural differences between groups. To characterize functional plasticity, we compared S1 responses to noxious laser stimuli of a fixed intensity between both groups and assessed the relationship between S1 activation and spontaneous pain in PHN patients. Although the intensity of evoked pain was comparable in both groups, PHN patients exhibited greater activation in S1 ipsilateral to the stimulated hand. Pain-related activity was identified in contralateral superior S1 (SS1) in controls as expected, but in bilateral inferior S1 (IS1) in PHN patients with no overlap between SS1 and IS1. Contralateral SS1 engaged during evoked pain in controls encoded spontaneous pain in patients, suggesting functional S1 reorganization in PHN. Resting-state fMRI data showed decreased functional connectivity between left and right SS1 in PHN patients, which scaled with the intensity of spontaneous pain. Finally, multivariate pattern analyses (MVPA) demonstrated that BOLD activity and resting-state functional connectivity of S1 predicted within-subject variations of evoked and spontaneous pain intensities across groups. In summary, functional reorganization in S1 might play a key role in chronic pain related to PHN and could be a potential treatment target in this patient group.

Dynamic Immune Landscape and VZV-Specific T Cell Responses in Patients With Herpes Zoster and Postherpetic Neuralgia.

ObjectivesVaricella-zoster virus (VZV) can induce herpes zoster (HZ) and postherpetic neuralgia (PHN). Immune cells play an important role in regulating HZ and PHN pathogenesis, but the dynamic immune profiles and molecular mechanisms remain unclear. This study aimed to screen dynamic immune signatures during HZ progression and elucidate the mechanism of VZV-specific T cells in PHN.MethodsWe used cytometry by time-of-flight (CyTOF) to analyze peripheral blood mononuclear cells (PBMC) samples from 45 patients with HZ and eight age-sex-matched healthy controls, eight PHN samples and seven non-PHN samples. Correlations between the immune subsets and clinical pain-related scores were performed. Further, the characteristics of VZV-specific T cells between PHN and non-PHN patients were evaluated by VZV peptide pools stimulation. The expression level of cytokines, including granzyme B, interleukin (IL)-2, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α was performed via cytometric bead array. Finally, we analyzed the alteration of Ca2+ signals in dorsal root ganglion (DRG)-derived cells after TNF-α stimulation.ResultsWe investigated the dynamic characteristics of the immune landscape of peripheral blood samples of patients with HZ and PHN, and depicted two major dynamic signatures in NK, CD4+ and CD8+ T subsets in patients with HZ, which closely correlated with clinical pain-related scores. The frequency of PD-1+CD4+ T cells, VZV-specific PD-1+CD4+ T cells, and the amount of TNF-α produced by VZV-specific T cells were higher in patients with PHN than without PHN. Furthermore, we showed that TNF-α could induce calcium influx in DRG-derived cells in a dose-dependent manner.ConclusionsOur results profiled the dynamic signatures of immune cells in patients with HZ and highlighted the important role of VZV-specific T cells in the pathogenesis of PHN.

Changing the paradigm in postherpetic neuralgia treatment: lidocaine 700 mg medicated plaster.

Chronic pain is currently considered a disease state with biopsychosocial consequences and a negative impact on patients' quality of life (QoL). Pain from postherpetic neuralgia (PHN) can persist for months or years and is a prototypical example of chronic pain. We analyzed PHN as a model of chronic pain, including its effects on QoL and clinical aspects. We explored treatment options, focusing on the topical treatment with lidocaine 700 mg medicated plaster (LMP) and how this impacts PHN management. This article is a narrative review of published studies. Preclinical and clinical studies were retrieved from literature through a search performed in PubMed/MEDLINE. To choose the appropriate treatment for chronic pains, such as PHN, not only efficacy but also tolerability, manageability, practicality, and compliance are important factors, especially in the long term. It is also important to set treatment expectations with the patients as total suppression of pain may be unrealistic, and a balance needs to be found between pain control and the minimization of adverse events. In this respect, LMP may be the best currently available treatment: it is easy to use, has low systemic absorption and thus a low risk for pharmacological interactions. Therefore, treatments can be personalized, and concomitant medications can be added, if needed. Recent data from a real-world study support this view by showing that LMP has superior effectiveness in reducing pain and improving the QoL compared to other commonly used systemic treatments and confirming its good tolerability profile that is mainly characterized by localized skin reactions. LMP is one of the best currently available treatment options for PHN patients balancing good efficacy with an excellent tolerability profile and can therefore be considered for use as a first-line treatment for PHN.

Associations of OPRM1 A118G Gene Polymorphism with Pain Sensitivity and Opioid Dosage of Patients with Postherpetic Neuralgia

This study aimed to explore the associations of OPRM1 A118G gene polymorphism with pain sensitivity and opioid dosage of patients with postherpetic neuralgia (PHN). According to the 3-month follow-up results, 103 PNH patients were enrolled as a PHN group, and 112 without PHN after herpes zoster were included as a non-PHN group. The factors affecting PHN occurrence were subjected to one-way analysis of variance and multivariate logistic regression analysis. The frequency distribution of GG, AG and AA genotypes in both PHN and non-PHN groups conformed to the Hardy-Weinberg equilibrium law (P&gt;0.05). Initial treatment duration of more than 72 hours, severe acute pain and genotype GG were independent risk factors for PHN. Genotype GG exhibited significantly increased distribution frequency in mild, moderate and severe PHN groups. The 48-hour opioid dosage was highest in the patients with genotype GG (P&lt;0.05). OPRM1 A118G gene polymorphism causes individual differences in the pharmacodynamics of opioids in PHN patients.

Cerebral structural alterations in the patients undergoing postherpetic neuralgia: A VBM-MRI study.

This study aimed to investigate the changes in gray matter (GM) volume and density in patients with postherpetic neuralgia (PHN). Using voxel-based morphometry (VBM), the differences in cerebral GM volume and concentration between 25 PHN patients and 25 healthy controls with similar gender ratios, ages, and education were compared. Meanwhile, correlation analysis was performed between the value of GM volume/concentration in the brain areas with discrepancy and the visual analog scale (VAS) score/lesion duration. The global GM volume in PHN patients was lower than that of healthy controls, while the total volume of cerebrospinal fluid in PHN patients was higher than that of healthy controls. In PHN patients, the GM volume decreased in the striatum, cerebellum, precentral gyrus, middle frontal gyrus, parahippocampal gyrus, postcentral gyrus, and so forth; the GM concentration decreased in the striatum, insula, middle and posterior cingulate, and superior temporal gyrus. There was a negative correlation between GM concentration in the right parahippocampal gyrus and the VAS in patients with PHN. In PHN patients, GM volume and density in the brain regions involved in nociceptive sensation, pain perception, and integration decreased significantly. The interaction between chronic pain of PHN and alteration of the cerebral structure may contribute to the occurrence and development of PHN.

Clinical significance of methyl-CpG binding protein 2 in postherpetic neuralgia: an observational study

The present study was aimed to investigate the clinical significance of methyl-CpG binding protein 2 (MECP2) in patients with postherpetic neuralgia (PHN). This prospective case control study enrolled 319 cases of PHN patients from April 2017~December 2019. The patients’ sleep quality and quality of life were evaluated using the Pittsburgh sleep quality score and the SF-36 scale, respectively. The serum levels of MECP2, CRP, IL-6 and TNF-α were tested using enzyme linked immunosorbent assay (ELISA). The pain condition of the patients was evaluated using the visual analogue scale (VAS). The levels of MECP2 were significantly increased in PHN patients compared with the patients without PHN. Serum MECP2 levels were the highest in patients with severe pain, and were the lowest in patients with mild pain. Similarly, the frequency of severe pain in patients with low expression of MECP2 was significantly lower than the patients with higher MECP2 expression. Besides, serum levels of inflammatory factors CRP, IL-6 and TNF-α were markedly increased in PHN patients, which were also increased with the increase of the severity of pain. CRP, IL-6 and TNF-α were positively correlated with serum levels of MECP2 in PHN patients. Before the study, patients with lower MECP2 levels showed a significantly higher SF-36 score and lower Pittsburgh and VAS scores than patients with higher levels of MECP2. However, after one month, no significant difference was found between the patients. ROC curve showed MECP2 had the potential as a diagnostic biomarker for PHN. In conclusion, higher serum MECP2 levels are associated with a more severe pain condition and increased release of inflammatory factors.

MRI Study of Cerebral Cortical Thickness in Patients with Herpes Zoster and Postherpetic Neuralgia

ObjectiveTo measure the changes in cerebral cortical thickness in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN) by surface-based morphometry (SBM) and further estimate its correlation with clinical scores.Materials and MethodsTwenty-nine HZ patients, 30 PHN patients and 30 well-matched healthy controls (HCs) were included. Magnetic resonance imaging (MRI) data from all subjects were collected and then analyzed by SBM. The changes in cortical thickness among the HZ, PHN and HC groups were analyzed by ANOVA and correlated with clinical scores.ResultsThe thickness of the bilateral primary visual cortex (V1, V2) and right primary visual cortex (V3), left somatosensory cortex (L3A), right anterior cingulate gyrus and medial prefrontal cortex (RS32) increased in PHN group, and the thickness the left insular and frontal opercular cortex (LFOP4), left motor cortex (L3B), and right superior temporal visual cortex (RSTV) were decreased in the HZ and PHN groups compared to the HC group. The thickness measurements of RS32, LFOP4, and (L3B) in HZ and PHN patients were correlated with the duration of disease. In HZ and PHN patients, the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores were significantly positively correlated.ConclusionChanges in cortical thickness in the areas related to sensory, motor, and cognitive/emotional changes in patients with PHN affect the neuroplasticity process of the brain, which may be the reason for the transformation of HZ into PHN and provide a possible explanation for the neuropathological mechanism of pain persistence in PHN patients.

Clinical efficacy of bulleyaconitine A combined with gabapentin on postherpetic neuralgia

Objective: To investigate the analgesic efficacy and safety of state-dependent sodium channel blocker-bulleyaconitine combined with calcium channel blocker-gabapentin on postherpetic neuralgia (PHN). Methods: A double-blind, randomized, placebo-controlled, parallel-group, multi-center study involving Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Qinghai Provincial People's Hospital, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, the Second Affiliated Hospital of Kunming Medical University was performed from September 2018 to December 2019. A total of 75 PHN patients were randomly divided into the experiment group (n=41) and the control group (n=34). On the basis of first-line treatment with gabapentin, the experiment group was given bulleyaconitine A tablets, while the control group was given placebo. The primary outcome was a 50% improvement in the visual analogue scale (VAS), and the effective rate of achieving the primary outcome between the two groups was compared; the Cox regression model was used to analyze the impact of related factors on the disease outcome. Secondary outcomes including scores of pain scales (ID-pain, DN4), Patient Health Questionnaire (PHQ-9), 7-item Generalized Anxiety Disorder (GAD-7) at 1, 2, 3, 4, 8, 12 weeks after treatment were applied to evaluate the efficacy and safety of the combination of bulleyaconitine A tablets with first-line drug in the treatment of PHN. Results: The effective rate was 68.3% (28/41) and the time reached the primary outcome was 28 (7, 84) days in the experiment group, while in the control group, the effective rate was 52.9% (18/34) and the time reached the primary outcome was 56 (14, 84) days. Cox regression analysis indicated that the grouping factor of oral bulleyaconitine A tablets was an independent factor for improving the outcome of PHN (HR=2.063, 95%CI: 1.059-4.018, P<0.05), and the probability of the experiment group reaching the primary outcome was 2.063 times that of the control group (P<0.05). Meanwhile, the outcome probability of the long disease course group (>6 months) was only 0.201 times that of the short disease course group (<6 months) (HR=0.201, 95%CI: 0.073-0.551, P<0.05). There was no statistically significant difference in the trend of VAS between the two groups (P>0.05). The scores of ID-pain, DN4, PHQ-9, and GAD-7 of the two groups were significantly improved compared with those before enrollment (P<0.05), but the differences between the two groups were not statistically significant (all P>0.05). Conclusion: Bulleyaconitine A tablet can promote the therapeutic efficacy of gabapentin, and improve the outcome of PHN in a short period of 3 months.

The brain\u2019s structural differences between postherpetic neuralgia and lower back pain

The purpose is to explore the brain’s structural difference in local morphology and between-region networks between two types of peripheral neuropathic pain (PNP): postherpetic neuralgia (PHN) and lower back pain (LBP). A total of 54 participants including 38 LBP and 16 PHN patients were enrolled. The average pain scores were 7.6 and 7.5 for LBP and PHN. High-resolution structural T1 weighted images were obtained. Both grey matter volume (GMV) and morphological connectivity (MC) were extracted. An independent two-sample t-test with false discovery rate (FDR) correction was used to identify the brain regions where LBP and PHN patients showed significant GMV difference. Next, we explored the differences of MC network between LBP and PHN patients and detected the group differences in network properties by using the two-sample t-test and FDR correction. Compared with PHN, LBP patients had significantly larger GMV in temporal gyrus, insula and fusiform gyrus (p < 0.05). The LBP cohort had significantly stronger MC in the connection between right precuneus and left opercular part of inferior frontal gyrus (p < 0.05). LBP patients had significantly stronger degree in left anterior cingulate gyrus and left rectus gyrus (p < 0.05) while had significantly weaker degree than PHN patients in left orbital part of middle frontal gyrus, left supplementary motor area and left superior parietal lobule (p < 0.05). LBP and PHN patients had significant differences in the brain’s GMV, MC, and network properties, which implies that different PNPs have different neural mechanisms concerning pain modulation.

Modulation of signal transduction gene expression following pulsed radiofrequency in dorsal root ganglia and pregabalin therapy.

Introduction: A randomized controlled study was conducted to assess modulation of signal transduction genes (PKA, PKC and ERK) following integrated multimodal approach encompassing pulsed radiofrequency treatment (PRF) of dorsal root ganglion and pregabalin in thoracic postherpetic neuralgia (PHN). Clinical variables such aspain intensity and quality of life werealso explored. Material & methods:A total of40 Patients of PHN were recruited. 20 patients randomly assigned to each of the two groups, group PP administered PRF with pregabalin and group SP administered pregabalin alone. Results: Significant downregulation of PKA and ERK observed in group PP at end of 10th week (p<0.05). A significantly positive correlation demonstrated between Visual analogscale scores and signal transduction genes expression in PHN patients. Conclusion: Downregulation of all three signal transduction genes was observed following the integrated multimodal approach; however, significant downregulation was observed with PKA and ERK only. A positive correlation observed between signal transduction gene expression and visual analogscale scores signify their role in the pathogenesis of PHN.

Immunological mechanism of postherpetic neuralgia and effect of pregabalin treatment on the mechanism: a prospective single-arm observational study.

BackgroundAlthough neuropathic pain is a severe and common pain, its pathophysiology has not been elucidated yet. Studies in recent years have focused on the immune system’s role in the pathogenesis of neuropathic pain. The aim of this study was to investigate the role of immunological mechanisms in neuropathic pain and the effect of pregabalin by measuring immunological marker levels in peripheral blood before and after pregabalin treatment in postherpetic neuralgia (PHN) patients with neuropathic pain.MethodsForty patients diagnosed with PHN were included in the study. CD4, T follicular cells (Tfh CD4+CXCR5+PD1+), Th17 (CD4+CCR6+ and CD4+IL17A+), regulatory T cells (Treg CD4+ CD25+foxp3+), Th1 (CD4+ CXCR3+ and CD4+ IFN-γ+) and Th2 (CD4+ IL-4+) cell ratios were measured in peripheral blood samples before treatment and after 3 months of treatment.ResultsWhen immunological marker and inflammation parameter levels were compared before and after treatment, the helper T cell ratio (CD3+, CD4+) was 30.28 ± 12.27% before treatment and 34.93 ± 11.70% after treatment, so there was a statistically significant increase (P = 0.028). Th17 was 4.75 ± 5.02% before treatment and 5.80 ± 3.13% after treatment, and there was a statistically significant increase (P = 0.036).ConclusionsImmunological mechanisms play an essential role in the pathogenesis of neuropathic pain, immunologically based treatment approach will be the critical point of treatment.

Abnormal within- and cross-networks functional connectivity in different outcomes of herpes zoster patients.

Neuroimaging studies have displayed aberrant brain activities in individual sensory- and emotional-linked regions in postherpetic neuralgia (PHN) patients. However, multi-dimensional dysfunction in chronic pain may rely on the interplay between networks. Little is known about the changes in the functional architecture of resting state networks (RSNs) in PHN. In this cross-sectional study, we recruited 31 PHN patients, 33 RHZ patients and 34 HCs; all participants underwent resting-state functional magnetic resonance imaging scans. We investigated the differences of within- and cross-network connectivities between different outcomes of HZ patients [including PHN and recuperation from herpes zoster (RHZ)] and healthy controls (HCs) so as to extract a characteristic network pattern of PHN. The abnormal network connectivities were then correlated with clinical variables in respective groups. PHN and RHZ patients could be similarly characterized by abnormal within-default mode network (DMN), DMN-salience network (SN) and SN-basal ganglia network (BGN) connectivity relative to HCs. Of note, compared with RHZ patients, PHN patients could be characterized by abnormal DMN-BGN and within-BGN connectivity. Furthermore, the within-DMN connectivity was associated with pain-induced emotional scores among PHN patients. Our study presented that network-level imbalance could account for the pain-related dysfunctions in different outcomes of herpes zoster patients. These insights are potentially useful for understanding neuromechanism of PHN and providing central therapeutic targets for PHN.

Assessment of Serum Vitamin D Levels in the serum of Patients with Postherpetic neuralgia and its correlation to pain severity: A cross‐sectional comparative study

Vitamin D is an essential micronutrient for the maintenance of many functions in the human body. Postherpetic neuralgia (PHN) is caused by the reactivation of the latent varicella-zoster virus (VZV) in the neurons. This study aims to assess the serum vitamin D level in patients with PHN and to correlate the level of vitamin D with pain severity. A hospital-based cross-sectional comparative study was conducted in the period from April 2019 to January 2021. One hundred and sixty-two individuals, matched for age and gender, divided into cases and controls (81 for each). Serum levels of 25(OH)D were measured for cases and controls. Demographic data were taken, and then the diagnosis of neuropathic pain in cases was established using the Douleur Neuropathique 4 (DN4) questionnaire. We included 39 (52%) males in the PHN group and 36 (48%) in the control group. There was no significant difference between groups regarding age, marital status, smoking and BMI. The duration of pain in our study had a mean of 7.6±3.6months. We found the DN4 score for the pain to be negatively associated with vitamin D levels (Pearson's correlation coefficient: -0.511,P=.000). The levels of vitamin D were moderately associated with pain duration (Pearson's correlation: -0.466,P=.000). PHN patients had a high prevalence of vitamin D deficiency and those who had vitamin D deficiency were older and had higher degrees of pain for a longer duration. In PHN patients, vitamin D deficiency was moderately associated with increased severity and duration of pain.

Lidocaine 700mg medicated plaster for postherpetic neuralgia: real-world data from the German Pain e-Registry.

Aim: To provide real-world evidence for the effectiveness and tolerability of lidocaine 700mg medicated plaster (LMP) compared with oral systemic first-line medications (OSM) in postherpetic neuralgia treatment. Patients & methods: Retrospective cohort study in patients refractory to at least one recommended OSM (single drug or a combination of drugs) using anonymized routine medical care data from the German Pain e-Registry. A matched pair approach using propensity score matching was employed. Results:A total of1711 datasets of postherpetic neuralgia patients were identified per treatment group. The majority (>60%) had experienced pain for more than a year and reported a high burden of pain and reduced quality of life. Six months of LMP treatment provided significantly greater pain reductions, improvements in pain-related impairments and quality of life than OSM treatment (p<0.001 for all parameters). Drug-related adverse eventsand treatment discontinuation due to drug-related adverse events also occurred less frequently under LMP treatment (p<0.001). Conclusion: These real-world data confirm the effectiveness and good tolerability of LMP under routine medical care. The treatment was significantly more effective when compared with first-line oral systemic medications.

Altered gray matter volume and functional connectivity in patients with herpes zoster and postherpetic neuralgia

Numerous neuroimaging studies on postherpetic neuralgia (PHN) and herpes zoster (HZ) have revealed abnormalities in brain structure/microstructure and function. However, few studies have focused on changes in gray matter (GM) volume and intrinsic functional connectivity (FC) in the transition from HZ to PHN. This study combined voxel-based morphometry and FC analysis methods to investigate GM volume and FC differences in 28 PHN patients, 25 HZ patients, and 21 well-matched healthy controls (HCs). Compared to HCs, PHN patients exhibited a reduction in GM volume in the bilateral putamen. Compared with HZ patients, PHN patients showed decreased GM volume in the left parahippocampal gyrus, putamen, anterior cingulate cortex, and right caudate and increased GM volume in the right thalamus. However, no regions with significant GM volume changes were found between the HZ and HC groups. Correlation analysis revealed that GM volume in the right putamen was positively associated with illness duration in PHN patients. Furthermore, lower FCs between the right putamen and right middle frontal gyrus/brainstem were observed in PHN patients than in HCs. These results indicate that aberrant GM volumes and FC in several brain regions, especially in the right putamen, are closely associated with chronification from HZ to PHN; moreover, these changes profoundly affect multiple dimensions of pain processing. These findings may provide new insights into the pathophysiological mechanisms of PHN.

Modulation of mRNA Expression of IL-6 and mTORC1 and Efficacy and Feasibility of an Integrated Approach Encompassing Cognitive Behavioral Therapy Along with Pregabalin for Management of Neuropathic Pain in Postherpetic Neuralgia: A Pilot Study.

This study was designed to explore the efficacy and feasibility of cognitive behavioral therapy (CBT) along with pregabalin and compare it with pregabalin monotherapy for the management of neuropathic pain in post-herpetic neuralgia (PHN) patients and to explore the modulation of messenger RNA (mRNA) expression of interleukin (IL)-6 and mammalian target of rapamycin-1 (mTORC1) genes in these patients. Randomized controlled pilot study. The patients aged >18 years of age with an established diagnosis of PHN with evident allodynia and hyperalgesia who had pain for at least 3 months after healing of rash with pain intensity ≥4/10 on NRS-Pain Scale were enrolled. The trial was registered with the Clinical Trials Registry-India (CTRI/2019/03/018014). A detailed baseline assessment regarding type and duration of pain and disability using pain-relevant self-report questionnaires was done. Two mL venous blood samples were collected for gene expression studies at base line and at end of 12 weeks of treatment. Patients were randomized into one of the two groups. Group PR received pregabalin and Group CP received CBT along with pregabalin. The pain intensity was measured using numeric rating scale (NRS)-Pain scale, neuropathic component of the pain by using Neuropathic Pain Symptom Inventory (NPSI) and Pain Detect Questionnaire (PDQ), sleep interference by NRS-Sleep, pain-related catastrophic thoughts by using Pain Catastrophizing Scale (PCS), depression and quality of life using Beck Depression Inventory-II (BDI-II) and Short Form-12 (SF-12), respectively. The research funding was supported by the intramural grant from the institution. A total of 40 patients with 20 in each group were included. Following integrated approach encompassing CBT and Pregabalin, group CP had significant downregulation of mRNA expression of IL-6; however, no such correlation was observed with mTOR expression. A significant decline in the intensity of pain, NPSI scoring for burning, allodynia, and pain-related catastrophizing were observed; also a significant improvement in depressive symptoms and quality of life were observed with the use of CBT. A significant downregulation of mRNA expression of IL-6 was observed; however, no significant correlation was observed between NRS pain score and ΔCt values of mRNA expression of both mTORC1 gene and IL-6 gene at baseline and at the end of 12th week. In addition, we note a significant decrease in pain intensity, depressive symptoms, and pain-related catastrophizing while improving QOL was observed with the use of CBT as a clinical adjunct along with pregabalin in PHN patients.

Collateral-pricking and blood-letting cupping combined with electroacupuncture for post-herpetic neuralgia: 刺络放血拔罐结合电针围刺治疗带状疱疹后神经痛临床观察

ObjectiveTo explore the clinical efficacy of collateral-pricking and blood-letting cupping combined with surrounding needling technique electroacupuncture in the treatment of post-herpetic neuralgia (PHN). MethodsSeventy-two patients with post-herpetic neuralgia were randomized into observation group and control group. Of the 72 cases, 12 cases fell off, so finally 30 cases in each group. The observation group was treated with collateral-pricking and blood-letting cupping combined with surrounding needling technique electroacupuncture, while the control group was treated simply with pregabalin capsules for 20 consecutive days. On the basis of the western medication pregabalin capsules, the same as that of the control group, collateral-pricking and blood-letting cupping combined with electroacupuncture in a surrounding needling technique, was adopted for the observation group, once every two days, ten days as one course of treatment, a total of two courses. The immediate visual analogue scale (VAS) before and after treatment were observed in the two groups, and their clinical effects were compared. ResultsThe VAS scores of PHN patients in the two groups after treatment were lower than those before treatment (both P<0.01), and the scores of observation group were lower than those of control group (P<0.05). The total effective rate of the observation group was 86.7%, higher than 73.3% of the control group. ConclusionThe clinical effect of collateral-pricking and blood-letting cupping combined with electroacupuncture is relatively satisfactory in the treatment of post-herpetic neuralgia.