Postherpetic Neuralgia Patients Research Articles

Long-Term Effects of Spinal Cord Stimulation on Pain in Postherpetic Neuralgia

Introduction: Postherpetic neuralgia (PHN) is a pain syndrome that develops within few months after the acute herpetic outbreak. The pain may be accompanied by specific cutaneous signs in the distribution of affected dermatomes and feel unbearable reaching up to 9–10/10 on visual analog scale (VAS). Despite the introduction of new medications, drug resistance develops in at least 50% of cases. Neuromodulation techniques such as spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) are considered as ones of the last resorts for PHN treatment, especially in pharmacoresistant patients. Recently, several studies with limited number of cases have shown high efficiency of neuromodulation (regression of pain syndrome in more than 82% of cases) after SCS in PHN patients, but these findings require further confirmation and have not been supported by large RCTs. Methods: Initially, 32 patients diagnosed with chronic drug-resistant PHN underwent a trial of SCS. Based on the trial results, a decision was made whether to implant a permanent SCS system. The condition of all patients implanted with SCS system was assessed using the VAS, SF-36, Patient Global Impression of Change (PGIC), and Medicine Quantification Scale, version III (MQS) questionnaires before the surgery and in the long-term follow-up. We also conducted systematic follow-up of patients who did not pass the test stimulation stage, using them as a control group to track the levels of pain. The hypothesis of normal distribution for quantitative values was tested using Shapiro-Wilk tests. Results: During the trial period, tonic spinal stimulation was effective in 16 out of 32 (50%) patients with drug-resistant PHN. Among 14 patients with implanted stimulators, a significant pain reduction (more than 50% from the baseline) was observed in 10 patients (71.4%). The pain level in patients with a tonic SCS was statistically lower than in patients receiving conservative therapy. For the entire group of patients with implanted SCS, a significant improvement was also observed in results of SF-36, PGIC, and MQS. Conclusion: Our clinical series demonstrates that tonic SCS was effective in 50% of patients with refractory PHN undergoing SCS trial. Significant improvement in pain control obtained during the long-term follow-up in patients treated with tonic SCS improves the quality of life and reduces the need for analgesic medications.

Intravenous patient-controlled analgesia with esketamine improves early depressive symptoms in patients with postherpetic neuralgia: a single-center retrospective cohort study

ObjectivePatients with Postherpetic Neuralgia (PHN) often exhibit depressive-like symptoms, significantly impacting their quality of life. Esketamine, known for its analgesic properties, has also been recognized for its rapid antidepressant effects. However, its efficacy in the treatment of PHN requires further exploration. This study aims to evaluate the impact of intravenous patient-controlled analgesia(PICA) with esketamine on depressive mood in PHN patients.MethodsThis retrospective study analyzed PHN patients hospitalized and treated at the affiliated hospital of Southwest Medical University from June 2021 to March 2023. Patients were divided into the esketamine group (E group) and the sufentanil group (S group) based on their treatment regimens. Primary outcomes included pain numerical rating scale(NRS), depression patient health questionaire-9(PHQ-9), and anxiety generalized anxiety disorder-7(GAD-7) scores measured before treatment, and at 3 days, 7 days, 1 month, 2 months, and 3 months post-treatment.ResultsA total of 83 patients were included in the analysis. Before treatment, there were no statistically significant differences in pain NRS, depression PHQ-9, and anxiety GAD-7 scores between the two groups (P > 0.05). Compared to before treatment, significant reductions in pain NRS scores were observed at all post-treatment time points in both groups (P < 0.05), with no differences between groups (P > 0.05). The E group exhibited significantly lower depression PHQ-9 scores than the S group at 3 days and 7 days post-treatment (P < 0.05), but no significant differences were observed at 1 month, 2 months, and 3 months (P > 0.05). Anxiety GAD-7 scores were significantly lower in the E group compared to the S group at 3 days, 7 days post-treatment (P < 0.05), with no statistical differences at 1 month, 2 months, and 3 months post-treatment (P > 0.05).ConclusionBoth PICA with esketamine and sufentanil alleviated pain equally in PHN patients. However, PICA with esketamine specifically improved early symptoms of anxiety and depression.

Altered Effective Connectivity of the Pain Matrix in Herpes Zoster and Postherpetic Neuralgia Patients: Granger Causality Analysis of Resting-State fMRI.

Shingles can cause long-term pain and negative emotions, along with changes in brain function. In this study, Granger Causality Analysis (GCA) was used to compare herpes zoster (HZ) and postherpetic neuralgia (PHN) differences in effective connections within the "pain matrix" between patients and healthy controls to further understand patterns of interaction between brain regions and explore the relationship between changes in effective connections and clinical features. Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 55 HZ; 55 PHN; and 50 age-, sex- matched healthy controls (HCs). The brain regions associated with the pain matrix are used as the seeds of effective connectivity. GCA was used to analyze effective connections in brain regions that differed significantly between groups. Then the correlation between GCA values and clinical indicators was studied. Compared with HC, GCA values between the thalamus and the amygdala, between the thalamus and the precentral gyrus, from the thalamus to the postcentral gyrus, and from the parahippocampal gyrus to the amygdala, anterior cingulate gyrus were significantly reduced in HZ patients. Compared with HC, GCA values between the insular and the postcentral gyrus, from the insular to the inferior parietal lobe, and from the postcentral gyrus to the amygdala were significantly reduced in PHN patients. Compared with HZ, GCA values between the inferior parietal lobe and the parahippocampal gyrus, between the inferior parietal lobe and the anterior cingulate gyrus, and from the anterior cingulate gyrus to the amygdala were significantly increased in PHN patients. The visual analogue scale (VAS) score of PHN patients was positively correlated with the GCA value from the central posterior lobe to the insula. PHN and HZ patients showed a broad reduction in effective connections, mainly reflected in abnormal pain pathway regulation, pain perception, negative emotion and memory production, providing new perspectives to understand the neuroimaging mechanisms of shingles.

Analysis of the efficacy and safety of pulsed radiofrequency for the treatment of thoracic postherpetic neuralgia in elderly patients with different pain phenotypes

Objective: To analyze the efficacy and safety of pulsed radiofrequency (PRF) for the treatment of thoracic postherpetic neuralgia (PHN) in elderly patients with different pain phenotypes. Methods: A total of 201 elderly thoracic PHN patients, including 110 males and 91 females aged (72.2±6.9) years who received high-voltage, long-duration PRF at the dorsal root ganglion at Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine from January 2020 to December 2022, were retrospectively included. The neuropathic pain symptom inventory (NPSI) was used to evaluate the five different pain phenotypes, which included superficial spontaneous pain, deep spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia, and to analyze the distribution of the five pain phenotypes. The numerical rating scale (NRS) and NPSI scores of all patients were compared before treatment and three months after treatment to evaluate the efficacy and safety of PRF for different pain phenotypes and pain phenotype combinations. Results: All patients had two or more pain phenotypes, and 50.2% (101/201) of the patients had five pain phenotypes at the same time. Compared with those before treatment, three months after treatment, the NPSI scores for superficial spontaneous pain, deep spontaneous pain, paroxysmal pain, evoked pain and paresthesia/dysesthesia decreased (all P<0.05), and the scores decreased by［M（Q1，Q3）］3.0 (2.0, 4.0), 1.5 (0.5, 2.5), 3.0 (2.5, 4.0), 2.3 (1.0, 4.0), and 1.0 (0.5, 2.0) points, respectively, the differences were statistically significant (P<0.001). The decrease in the NPSI score in patients with paroxysmal pain was greater than that in patients with the other 4 pain phenotypes (all P<0.05). After treatment, the NRS score decreased by 4.0 (3.0, 5.0), 4.0 (3.0, 5.0), 4.0 (3.0, 5.0) and 5.0 (4.0, 6.0) points in patients with 2, 3, 4 and 5 pain phenotypes, respectively, and the difference was statistically significant (P<0.001). The decrease in the NRS score was greater in patients with a combination of 5 pain phenotypes than that in patients with a combination of 3 and 4 pain phenotypes (all P<0.05). No complications, such as pneumothorax, haematoma or infection, occurred in any of the patients during treatment. Conclusion: PRF has different therapeutic effects on PHN patients with different pain phenotypes, it has the best effect on paroxysmal pain, and the treatment is safe.

Outcomes of Twice Repeated High-Voltage Long-Duration Pulsed Radiofrequency Treatment in Subacute Postherpetic Neuralgia: a Retrospective Single-Center Analysis.

The treatment of herpes zoster-related pain is challenging, and requires a variety of methods including pulse radio frequency modulation. Among them, single-time high-voltage long-term pulsed radiofrequency (HL-PRF) has been proved to be an effective treatment for subacute postherpetic neuralgia. However, it has the possibility of poor long-term curative effect and recurrence of neuralgia. In this study, we aim to identify the clinical efficacy and safety of twice repeated HL-PRF treatment in patients with subacute postherpetic neuralgia. We conducted a retrospective analysis of subacute postherpetic neuralgia patients who underwent HL-PRF treatment. Pain Management Department of First Affiliated Hospital of Wannan Medical College. We enrolled all patients with subacute postherpetic neuralgia, who underwent HL-PRF treatment from January 2023 to October 2023. The primary outcome variable was the visual Analog Scale (VAS) scores at 1, 4, 8, and 12 weeks after treatment. Secondary outcomes included Pittsburgh sleep quality index (PSQI), 36-item short-form health survey (SF-36) score, and total effective rate after treatment. A total of 63 patients were included in the analysis. Among them, 33 patients received single-time HL-PRF treatment (Group S) and 30 patients received twice repeated HL-PRF treatment (Group T). Pain scores, PSQI scores, and SF-36 score were reduced in both groups after treatment (P < 0.001). Compared to group S, the VAS scores, PSQI scores, anxiety scores, and depression scores were significantly lower at 1, 4, 8, and 12 weeks in group T. (P < 0.001). The total efficiency rate at 12 weeks after treatment of group T was statistically higher than that of group S (60.6% vs 86.7%, P < 0.05). Twice repeated high-voltage long-duration PRF therapy demonstrates satisfactory efficacy in patients with subacute postherpetic neuralgia and is associated with no significant adverse reactions.

Bone morphogenetic protein 4 derived from the cerebrospinal fluid in patients with postherpetic neuralgia induces allodynia via the crosstalk between microglia and astrocyte

IntroductionDuring postherpetic neuralgia (PHN), the cerebral spinal fluid (CSF) possesses the capability to trigger glial activation and inflammation, yet the specific changes in its composition remain unclear. Recent findings from our research indicate elevations of central bone morphogenetic protein 4 (BMP4) during neuropathic pain (NP), serving as an independent modulator of glial cells. Herein, the aim of the present study is to test the CSF-BMP4 expressions and its role in the glial modulation in the process of PHN. MethodsCSF samples were collected from both PHN patients and non-painful individuals (Control) to assess BMP4 and its antagonist Noggin levels. Besides, intrathecal administration of both CSF types was conducted in normal rats to evaluate the impact on pain behavior, glial activity, and inflammation.; Additionally, both Noggin and STAT3 antagonist-Stattic were employed to treat the PHN-CSF or exogenous BMP4 challenged cultured astrocytes to explore downstream signals. Finally, microglial depletion was performed prior to the PHN-CSF intervention so as to elucidate the microglia-astrocyte crosstalk. ResultsBMP4 levels were significantly higher in PHN-CSF compared to Control-CSF (P < 0.001), with a positive correlation with pain duration (P < 0.05, r = 0.502). Comparing with the Control-CSF producing moderate paw withdrawal threshold (PWT) decline and microglial activation, PHN-CSF further exacerbated allodynia and triggered both microglial and astrocytic activation (P < 0.05). Moreover, PHN-CSF rather than Control-CSF evoked microglial proliferation and pro-inflammatory transformation, reinforced iron storage, and activated astrocytes possibly through both SMAD159 and STAT3 signaling, which were all mitigated by the Noggin application (P < 0.05). Next, both Noggin and Stattic effectively attenuated BMP4-induced GFAP and IL-6 upregulation, as well as SMAD159 and STAT3 phosphorylation in the cultured astrocytes (P < 0.05). Finally, microglial depletion diminished PHN-CSF induced astrogliosis, inflammation and endogenous BMP4 expression (P < 0.05). ConclusionOur study highlights the role of CSF-BMP4 elevation in glial activation and allodynia during PHN, suggesting a potential therapeutic avenue for future exploration.

Humoral Cytokine Levels in Patients with Herpes Zoster: A Meta-Analysis.

The neurocutaneous disease caused by the reactivation of varicella-zoster virus (VZV) is called herpes zoster (HZ). The virus remains in the spinal cord back root after the chickenpox disappears. Diminished immune function can reactivate VZV, causing severe neuropathic pain that can last for months or even years, leading to postherpetic neuralgia (PHN), which severely affects the patient's quality of life. Much literature compares various cytokine levels in the body fluids HZ and PHN patients; however, no studies comprehensively evaluate them. The Cochrane Library, PubMed, Web of Science, and Medline were screened for studies on cytokine levels in body fluids of HZ and PHN patients in the English language. Healthy individuals were selected as the control group, and the standardized mean difference (SMD) between the case and control groups was imputed using a fixed-effects or random-effects model and expressed as a 95% confidence interval (CI). The Newcastle-Ottawa Scale (NOS) was used to assess article quality. This meta-analysis included 13 articles with 1373 participants. Compared with the control group, the HZ group had significantly higher levels of interleukin (IL)-4, IL-6, IL-10, Hcy, and C-reactive protein (CRP), whereas the levels of CD3+ T and CD4+ T lymphocytes were reduced. Additionally, PHN patients had significantly higher levels of IL-6 and IL-1β compared with the control group. This meta-analysis provides compelling evidence that CRP, Hcy, IL-1β, IL-4, IL-6, IL-8, and IL-10 are associated with the genesis and development of HZ and PHN. These markers can be used to improve the diagnosis and treatment of these diseases.Furthermore, for making the results more convincing, it is necessary to harmonize sample acquisition techniques and analytical methods and also require larger, more rigorously designed studies with broader subgroups and sex/age-matched controls.

Efficacy of Modified Jaipur Block in Post Herpetic Neuralgia

Post herpetic neuralgia (PHN), a chronic neuropathic pain arising after herpes zoster (shingles) infection is notable, if discomfort persists beyond 90 days from the initial outbreak. Objective: To determine the efficacy of Modified Jaipur Block in reducing pain in patients with Post Herpetic Neuralgia. Methods: An uncontrolled clinical trial at Sheikh Zayed Hospital, Rahim Yar Khan, from January 2023 to September 2023 included 103 post herpetic neuralgia patients aged 20-80 years. Pain severity assessed using VAS score at baseline and follow-ups; efficacy defined as &gt;75% decrease in VAS pain score at 6 months. Statistical analysis utilized SPSS 26.0, employing paired t-tests and Chi-square tests for efficacy and subgroup analyses. Results: In 103 patients predominantly aged 51-65 years and suffering mainly from thoracic pain, the Modified Jaipur block treatment yielded substantial reductions in Visual Analogue Scale (VAS) scores. From an initial mean VAS of 8.15±1.389, scores declined significantly to 2.66±2.379 at the last follow-up (p&lt;0.001). A notable 73.8% of patients achieved remission, while relapses were observed in 7.8%. No association between remission rates and demographic or clinical variables was detected (p&gt;0.05). At the 6-month follow-up, 61.2% of patients demonstrated efficacy (over 75% reduction in VAS pain scores), with a significantly higher efficacy noted in cases of intermittent pain (p&lt;0.05). Conclusions: The Modified Jaipur block treatment demonstrated significant efficacy in pain reduction. The study underscores the potential of this treatment modality for targeted pain management.

Disrupted Balance of Short- and Long-Range Functional Connectivity Density in Patients with Herpes Zoster or Postherpetic Neuralgia: A Resting-State fMRI Study.

This study aimed to explore the abnormal changes in short- and long-range functional connectivity density (FCD) in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN). Twenty HZ patients, 22 PHN patients, and 19 well-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scans. We used FCD mapping, a data-driven graph theory method, to investigate local and global functional connectivity patterns. Both short- and long-range FCD were calculated and compared among the PHN, HZ, and HC groups. Then, the abnormal regions were used to calculate seed-based functional connectivity. Finally, correlation analyses were performed between the altered FCD values and clinical datas. Compared with HCs, HZ patients showed significantly increased long-range FCD of the bilateral cerebellum, thalamus, parahippocampal gyrus, superior temporal gyrus and lingual gyrus. HZ patients also displayed significantly decreased short-range FCD of the bilateral posterior cingulate gyrus, median cingulate/paracingulate gyri, and left precuneus. Compared with HCs, PHN patients displayed significantly decreased long-range FCD of the bilateral superior frontal gyrus and decreased short-range FCD in the bilateral posterior cingulate gyrus, median cingulate/paracingulate gyri, and precuneus. However, there was no significant difference in either long-range or short-range FCD between the PHN and HZ patients. Long-range FCD deficit areas and the right insula showed altered functional connectivity in PHN patients. Furthermore, pain duration in patients with PHN was correlated with abnormal long-range FCD. Herpes zoster pain widely affects intra- and inter-regional functional connectivity, leading to disrupted short-range FCD and increased long-range FCD during different stages of the disease. Long-term chronic pain in PHN patients may impair the pain emotion regulation pathway. These findings could improve our understanding of the pathophysiological mechanisms of HZ and PHN and offer neuroimaging markers for HZ and PHN.

The relationship between pain duration characteristics and pain intensity in herpes zoster-related pain: a single-center retrospective study.

The varicella-zoster virus (VZV) can cause herpes zoster (HZ), which may progress to postherpetic neuralgia (PHN), leading to severe inflammatory responses and pain. This study investigates the relationship between pain duration characteristics and pain intensity in patients with herpes zoster-related pain, hypothesizing that persistent pain correlates with higher pain intensity compared to intermittent pain. A retrospective study was conducted at the Second Affiliated Hospital of Guangxi Medical University, China. Data from patients treated for herpes zoster-related pain between January 2019 and February 2024 were analyzed. Pain intensity was measured using the Numerical Rating Scale (NRS-11), and pain duration was categorized as intermittent or persistent. Multivariate regression models were used to assess the association between pain duration and intensity, adjusting for potential confounders. A total of 840 patients were included. Persistent pain was significantly associated with higher NRS-11 scores compared to intermittent pain (β = 0.71, 95% CI 0.50-0.91, p < 0.001). Subgroup analyses showed that persistent pain was associated with higher pain intensity in both acute HZ and PHN patients (HZ: β = 0.71, 95% CI 0.45-0.96, p < 0.001; PHN: β = 0.76, 95% CI 0.40-1.13, p < 0.001). Inflammatory markers, such as C-reactive protein (CRP) and white blood cell count, were positively correlated with pain intensity. Pain duration significantly impacts pain intensity in HZ patients. Considering pain duration is crucial for effective pain management. Further research should explore the mechanisms underlying persistent pain to develop better treatment strategies.

Impact of Herpes Zoster and Postherpetic Neuralgia on the Quality of Life in China: A Prospective Study.

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

Exploring blood transcriptomic signatures in patients with herpes zoster and postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a common, severe, and hard-to-treat chronic pain condition in clinics. Although PHN is developed from herpes zoster (HZ), the developing mechanism is unknown. A previous study investigated blood metabolomic and proteomic profiling in patients with PHN and HZ. The current study aims to explore the blood transcriptomic signature of PHN compared to HZ patients. Whole blood from eight PHN and 15 HZ patients was used for RNA-Seq analysis. There were 82 and 1,788 genes detected specifically in the PHN and HZ groups, respectively. PHN-specific genes are involved in viral infection, lipid and carbohydrate metabolism, and immune response. For genes coexpressed in PHN and HZ patients, there were 407 differential expression genes (DEGs), including 205 upregulated (UP DEGs) and 202 downregulated (DOWN DEGs) in PHN compared to HZ groups. DEGs are involved in viral infection, type I interferon (IFN), and hemoglobin and oxygen carrier activity. UP DEGs are associated with regulatory T cells (Tregs), activated NK cells, and neutrophils, while DOWN DEGs are associated with Tregs, resting NK cells, and monocytes. The results suggest that the metabolism of lipid, glycan, and nucleotides, type I IFN signaling, and altered neutrophil activation are associated with and might contribute to the development of PHN in HZ. It is also suggested that persistent or altered activation of nonspecific immunity may contribute to the development of PHN from HZ.

A follow-up study on the pain changes trend and effects in patients diagnosed with herpes zoster in Beijing City

Objective: To understand the changes in pain and its effects in patients with the diagnosis of herpes zoster. Methods: A total of 3 487 patients diagnosed with herpes zoster (HZ) for the first time at the outpatient department of Miyun District Hospital from January 1, 2017, to December 31, 2019, were included in the study. The information of patients was registered and issued with a record card. Patients were required to record the time of pain and rash by themselves. Telephone follow-up was conducted at 21, 90, 180 and 365 days after the onset of rashes, including hospitalization, location of rash and pain, and the time of start and end. The impact of pain on life was evaluated by the Zoster Brief Pain Inventory (ZBPI). Results: The age of 2 999 HZ patients included in the analysis were (53±16) years old, including 1 377 (45.91%) males and 1 903 (63.45%) patients aged 50 years and older. After 21 days of rash, mild, moderate and severe pain accounted for 20.87% (626 cases), 37.98% (1 139 cases) and 33.81% (1 014 cases), respectively. Only 5.07% (152 cases) had no pain or discomfort, and 2.27% (68 cases) had no pain but discomfort. Most of the pain sites were consistent with the rash sites. The chest and back and waist and abdomen were the most common, accounting for 35.58% (1 067 cases) and 29.18% (875 cases), respectively, followed by the limbs and face and neck, accounting for 16.74% (502 cases) and 16.40% (492 cases), respectively. The M (Q1, Q3) of pain days in the HZ patients was 14 (8, 20) days, and the incidence of post-herpetic neuralgia (PHN) was 6.63% (171/2 580) (excluding 419 patients who refused to visit or lost to visit on 90 days after the onset of rash). The pain score of HZ patients within 21 days after the rash was (5.19±2.73) points, and the pain score of PHN patients was (7.61±2.13) points, which was significantly higher than that of non-PHN patients [(5.04±2.69) points] (P<0.001). Daily activities, emotions, walking ability, work, social interaction, sleep and recreation were affected for 21 days after the rash in HZ patients, ranging from 60.79% to 83.83%, with sleep being the most affected (83.83%). The impact scores of pain and life dimensions in PHN patients ranged from 4.59 to 7.61 points on the ZBPI scale, which were higher than those in non-PHN patients (2.49-5.04) (t values ranged from 8.86 to 11.67, all P values <0.001). Conclusion: The proportion of pain in HZ patients after the diagnosis is high, and the pain is more obvious in patients with PHN and HZ patients aged 50 and older, which has a greater impact on their daily lives.

Cerebrospinal Fluid Proteomic Profiles in Patients with Postherpetic Neuralgia.

The intrinsic mechanism of postherpetic neuralgia (PHN) remains unclear. Herein, we aimed to seek the hub proteins in the cerebrospinal fluid (CSF), which display significant changes between the PHN and nonpainful patients (Control). First, the proteomic results showed that compared with the Control-CSF, there were 100 upregulated and 50 downregulated differentially expressed proteins (DEPs) in the PHN-CSF. Besides, functional analyses including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) revealed that biological processes and pathways including complement activation, infection, coagulation, and lipid metabolism were activated, while synaptic organization was suppressed. Next, the protein-protein interaction (PPI) analysis indicated that increased PLG, F2, APOA1, APOA2, SERPINC1, and KNG1 and reduced APOE, which were all enriched in the top pathways according to the KEGG analysis, were defined as hub proteins. Finally, three of the hub proteins, such as PLG, APOA1, and APOE, were reconfirmed in a larger cohort using both enzyme-linked immunosorbent assay (ELISA) and Western blotting methods. Above all, the results indicated that PLG, APOA1, and APOE and their involved processes such as infection, inflammation, cholesterol metabolism, and coagulation shall be potential therapeutic approaches. (The raw mass spectrometry proteome data and search results have been deposited to the iProx-integrated Proteome Resources (http://www.iprox.cn) with the data set identifier IPX0007372000.).

Aberrant functional and causal connectivity of the amygdala in herpes zoster and post-herpetic neuralgia patients.

Resting-state functional magnetic resonance imaging (rs-fMRI) and Granger causality analysis (GCA) were used to observe the characteristics of amygdala and whole-brain effect connections in patients with herpes zoster (HZ) and post-herpetic neuralgia (PHN) and to determine their relationship with clinical features. Rs-fMRI scans were performed on 50 HZ; 50 PHN; and 50 age-, sex- and education-year-matched healthy controls (HCs). Bilateral amygdala subregions were used as seeds for functional connectivity (FC). GCA was used to analyze the effective connection of brain regions that were significantly different among groups. Then, the correlation between FC, and GCA values and clinical indices was investigated. PHN had impaired FC between the amygdala subregion with the putamen, cortex, anterior cingulate cortex (ACC) to HCs and reduced FC of medial amygdala (MeA) with the parieto-occipital lobe and motor cortex to HZ; HZ had reduced FC of the lateral amygdala (LA) with the insula to HCs. GCA values from the bilateral LA to the bilateral ACC, left MeA to the bilateral ACC and left putamen, and right ACC to the bilateral MeA were reduced in PHN patients compared to HCs. Compared with HCs, the GCA values from the left MeA to the left ACC and right putamen were reduced in HZ. The GCA values from the amygdala subregion to the ACC were positively correlated with HAMA or HAMD scores in PHN. PHN showed reduced FC between the amygdala subregions and cortico-putamen and decreased effective connectivity from the amygdala subregion to the ACC and putamen. HZ and PHN patients had significant changes in effective connectivity in brain regions, including diverse functional areas emanating from and projecting to the amygdala. The current findings will provide a new perspective for understanding the neuropathophysiological mechanism HZ and PHN.

Alteration of static and dynamic intrinsic brain activity induced by short-term spinal cord stimulation in postherpetic neuralgia patients.

Short-term spinal cord stimulation (stSCS) is an effective treatment for postherpetic neuralgia (PHN). However, how exactly stSCS affects time-dynamic intrinsic brain activity in PHN patients is not clear. The purpose of this study was to examine the static and dynamic variability of neural activity in PHN patients after stSCS. In this study, 10 patients with PHN underwent resting-state functional magnetic resonance imaging (rs-fMRI) at baseline and after SCS. The amplitude of low-frequency fluctuations (ALFF) and dynamic ALFF (dALFF) were used to investigate the static and dynamic variability of neural activity in PHN patients after stSCS. We additionally examined the associations between clinical parameters and functional changes in the brain. There was a significant increase in dALFF in the left precuneus and right superior parietal gyrus, and a decrease in dALFF in the left inferior temporal gyrus, right gyrus rectus, left superior temporal gyrus, right orbitofrontal cortex, and left orbitofrontal cortex. There was significantly increased ALFF in the right inferior temporal gyrus, and decreased ALFF in the right lingual gyrus, left superior parietal gyrus, right superior parietal gyrus, and left precuneus. Furthermore, Pittsburgh sleep quality index scores were positively associated with dALFF changes in the left superior temporal gyrus and left orbitofrontal cortex. Hospital anxiety and depression scale scores and continuous pain scores exhibited significant negative correlation with dALFF changes in the right superior parietal gyrus. This study indicated that stSCS is able to cause dALFF changes in PHN patients, thus stSCS might alter brain functions to relieve pain, sleep, and mood symptoms. The findings provide new insights into the mechanisms of stSCS efficacy in the treatment of patients with PHN.

Alterations of the gut microbiota in patients with postherpetic neuralgia

Postherpetic neuralgia (PHN) is a prevalent, intricate, and intractable form of neuropathic pain. The available evidence indicates that alterations in the gut microbiota are significant environmental determinants in the development of chronic neuropathic pain. Nevertheless, the correlation between the gut microbiota and PHN remains elusive. A cross-sectional study was performed on a cohort of 27 patients diagnosed with PHN and 27 matched healthy controls. Fecal samples were collected and subjected to microbiota analysis using 16S ribosomal RNA gene sequencing. Comparable levels of bacterial richness and diversity were observed in the gut microbiota of PHN patients and healthy controls. A significant difference was observed in 37 genera between the two groups. Furthermore, the LEfSe method revealed that the abundance levels of Escherichia-Shigella, Streptococcus, Ligilactobacillus, and Clostridia_UCG-014_unclassified were elevated in PHN patients, while Eubacterium_hallii_group, Butyricicoccus, Tyzzerella, Dorea, Parasutterella, Romboutsia, Megamonas, and Agathobacter genera were reduced in comparison to healthy controls. Significantly, the discriminant model utilizing the predominant microbiota exhibited efficacy in distinguishing PHN patients from healthy controls, with an area under the curve value of 0.824. Moreover, Spearman correlation analysis demonstrated noteworthy correlations between various gut microbiota and clinical symptoms, including disease course, anxiety state, sleep quality, heat pain, pain intensity, and itching intensity. Gut microbiota dysbiosis exists in PHN patients, microbiome differences could be used to distinguish PHN patients from normal healthy individuals with high sensitivity and specificity, and altered gut microbiota are related to clinical manifestations, suggesting potentially novel prevention and therapeutic directions of PHN.

Decreased Functional Connectivity of the Core Pain Matrix in Herpes Zoster and Postherpetic Neuralgia Patients.

The purpose of this study was to explore the resting-state functional connectivity (FC) changes among the pain matrix and other brain regions in herpes zoster (HZ) and postherpetic neuralgia (PHN) patients. Fifty-four PHN patients, 52 HZ patients, and 54 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. We used a seed-based FC approach to investigate whether HZ and PHN patients exhibited abnormal FC between the pain matrix and other brain regions compared to HCs. A random forest (RF) model was constructed to explore the feasibility of potential neuroimaging indicators to distinguish the two groups of patients. We found that PHN patients exhibited decreased FCs between the pain matrix and the putamen, superior temporal gyrus, middle frontal gyrus, middle cingulate gyrus, amygdala, precuneus, and supplementary motor area compared with HCs. Similar results were observed in HZ patients. The disease durations of PHN patients were negatively correlated with those aforementioned impaired FCs. The results of machine learning experiments showed that the RF model combined with FC features achieved a classification accuracy of 75%. Disrupted FC among the pain matrix and other regions in HZ and PHN patients may affect multiple dimensions of pain processing.

Clinico-Epidemiological Profile of Immunocompetent Patients Diagnosed with Herpes Zoster: A Single-Center Retrospective Cohort Study from Sinop

Aim: Herpes zoster (HZ) mainly occurs in immunocompetent individuals, even though immunosuppression&#x0D; is a well-known risk factor. The aim of this study was to evaluate the demographic and clinical features&#x0D; of immunocompetent HZ patients and HZ-related complications with a special focus on possible&#x0D; contributing factors.&#x0D; Material and Methods: This single-center, retrospective cohort study included 98 patients with no&#x0D; known immunosuppressive condition out of 103 patients diagnosed with HZ between September 2019&#x0D; and August 2020. The patients were evaluated in terms of age, sex, medical history, clinical features,&#x0D; triggering factors, seasonality, complications, and neutrophil-to-lymphocyte ratio (NLR) as a marker of&#x0D; systemic inflammation.&#x0D; Results: Ninetyeight immunocompetent patients (male:female ratio=1.1:1) were diagnosed with HZ,&#x0D; with a median age of 59 years (age range: 5-88). Thoracic dermatome was the leading dermatome&#x0D; (n=45). Trigeminal nerve was involved in 11 patients, eight of them presenting with ophthalmic HZ. HZ&#x0D; attacks were mainly detected in summer, while ophthalmic HZ cases were exclusively diagnosed during&#x0D; fall and winter. Two patients developed ophthalmic HZ following trauma. Eleven patients experienced&#x0D; postherpetic neuralgia (PHN) during follow-up with a male predominance (p=0.009). A higher mean NLR&#x0D; value was detected in PHN patients, although it was not statistically significant (p=0.136).&#x0D; Conclusion: The findings of our study are compatible with the current literature regarding the main&#x0D; presentation pattern of HZ as unilateral thoracic dermatome involvement and the complications such as&#x0D; PHN and ophthalmic HZ occurring in a subgroup of patients. The high HZ incidence rate in our series is&#x0D; likely due to the high median age of the population in our region. The summer peak of HZ cases further&#x0D; supports the seasonal variability due to the ultraviolet effect, whereas mechanical trauma is another&#x0D; possible triggering factor. The predictive value of NLR for PHN should be evaluated in further studies.

Evaluation of the correlation of dorsal root ganglia and spinal nerves with clinical symptoms in patients with postherpetic neuralgia using magnetic resonance neurography.

To assess changes of dorsal root ganglia (DRG) and spinal nerves in patients with postherpetic neuralgia (PHN), and investigate the correlation between DRG morphology and clinical symptoms in PHN patients using magnetic resonance neurography (MRN). In this case-control study, forty-nine lesioned DRG in 30 patients and 49 normal DRG in 30 well-matched (age, sex, height, weight) healthy controls were assessed. Clinical symptoms of patients (pain, allodynia, itching, and numbness) were assessed. MRN features (DRG volume (VDRG), the largest diameter (Dmax) of spinal nerves, signal intensity of DRG and spinal nerves (M-value)) were measured in all participants. Multilinear regression analysis was used to evaluate the relationship between the DRG morphology and clinical symptoms in patients. The volume and relative M-value of lesioned DRG in patients were significantly higher than those on the same side of healthy controls (p = 0.013, p < 0.001, respectively). The mean Dmax and relative M-value of spinal nerves on the lesioned side were significantly higher than those on the contralateral and same side of healthy controls (p < 0.0001, p = 0.0001, p = 0.0011, p = 0.0053, respectively). No difference was found between the mean VDRG of the lesioned and contralateral sides. Multiple linear regression analysis revealed that disease duration was independent risk factor for the maximum rate of VDRG differences (p = 0.013). DRG and spinal nerves on the lesioned side are swollen during PHN. Disease duration is an independent risk factor for morphological differences in the lesioned DRG of PHN patients. This study provides important guidance for individualized treatments of PHN.