Postherpetic Neuralgia Patients Research Articles

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.

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.

Effect of extracorporeal shock wave combined with pregabalin on patients with post-herpetic neuralgia.

Post-herpetic neuralgia (PHN) is a chronic pain that is difficult to treat and lasts a long time, which poses a threat to patients' physical and mental health (MH) and quality of life. To analyze the effectiveness of extracorporeal shock wave (ESW) combined with pregabalin on PHN and its impact on PHN patients' quality of life with the help of a random number table. Totally 164 PHN patients were assigned to a control group (n = 82) or an observation group (n = 82). The observation group was given pregabalin combined with ESW treatment, while the control group was only given pregabalin. In the 2 groups, the general clinical data of the patients were compared. The inflammation levels including erythrocyte sedimentation rate (ESR), CRP, lymphocyte count and albumin level in both groups were compared prior to and following therapy. In addition, the difference between pretreatment and post-treatment in the 2 groups was compared with respect to neuralgia and quality of life. After treatment, the observation group exhibited much lower ESR and CRP but quite higher lymphocyte count and albumin level relative to the control group (P < .05). Additionally, the improvement in visual analogue scale (VAS) scores and short form 36 (SF-36) scale scores including role-emotional (RE), MH, physical function (PF), general health (GH), bodily pain (BP), social function (SF), vitality (VT), and role-physical (RP) scores in the 2 groups were pronounced following treatment, which was more apparent in the observation group (P < .05). The combination of ESW with pregabalin can reduce the inflammation, improve the quality of life of PHN patients and effectively relieve their neuralgia.

Laser speckle contrast imaging to predict the effect of temporary spinal cord stimulation in postherpetic neuralgia patients: A prospective observational study

Temporary spinal cord stimulation (tSCS) can effectively reduce the pain and severity of postherpetic neuralgia (PHN). However, there are no effective and objective methods for predicting the effects of tSCS on PHN. Laser speckle contrast imaging (LSCI) is frequently used in neurology to evaluate the effectiveness of treatment. To assess the accuracy of LSCI in predicting the impact of tSCS on PHN, 14 adult patients receiving tSCS treatments for spinal nerve-innervated (C6-T2) PHN participated in this observational study. Visual analog scale (VAS) assessments and LSCI blood flow images of the fingers were recorded after the tSCS procedure. The results showed that the VAS scores of all patients decreased significantly. Moreover, the blood flow index (BFI) values were significantly higher than they were before the procedure. Increased blood flow and pain alleviation were positively correlated. The findings indicated that spinal nerve PHN (C6-T2) was significantly reduced by tSCS. Pain alleviation by tSCS was positively correlated with increased blood flow in the hand. The effect of tSCS on PHN may thus be predicted using an independent and consistent indicator such as LSCI.

Randomized, Placebo-Controlled, Multicenter Clinical Study on the Efficacy and Safety of Lidocaine Patches in Chinese Patients with Postherpetic Neuralgia.

To evaluate the efficacy and safety of lidocaine patches in Chinese patients with postherpetic neuralgia (PHN). Patients were randomized to receive lidocaine patches or placebo every day for 4weeks. Efficacy endpoints included the decrease of analogue scale score (VAS) value at week 4, 2 and 1 and the percentage of patients that achieved a 30% decrease of VAS value. Safety analyses were conducted as well. Two hundred forty Chinese patients were randomized. At week 1, lidocaine patch-treated patients had a higher clinical response versus placebo, and at week 4, the mean (SD) decreases of VAS value compared to the baseline were 14.01 (14.35) in the treatment group and 9.36 (12.03) in the placebo group (p = 0.0088). Overall, the safety profile in the treatment group was consistent with that observed in the placebo group [adverse event (AE) incidence rate: 33.33% versus 37.29%, p = 0.5857]. Lidocaine patches resulted in improved clinical response versus placebo in the treatment of PHN patients and were well tolerated.

Effects of Intradermal Botulinum Toxin Injections on Herpes Zoster Related Neuralgia.

Postherpetic neuralgia (PHN), which represents the most common chronic complication of herpes zoster, is characterized by intense pain and is difficult to treat. In fact, no treatments are currently available that can effectively reduce the pain associated with PHN. Recent evidence has been presented indicating that Botulinum toxin (BoNT-A) can serve as an effective and safe treatment for peripheral neuropathic pain. The effects of intradermal BoNT-A injections on herpes zoster related neuralgia were investigated in this study. Patients diagnosed with herpes zoster related acute neuralgia (N=13 - acute group) and those diagnosed with postherpetic neuralgia (N=17 - PHN group) were enrolled in this study. The two groups were treated with intradermal injections of BoNT-A at the site of their affected pain areas and were then assessed at 1 day, 1 week, 2 weeks, 1 month, 2 months and 3 months after their BoNT-A treatments. When compared with pre-treatment values, Visual Analogue Scores (VAS) in all patients were all significantly decreased at all times tested following BoNT-A injection. Before treatment, PHN patients had significantly higher VAS than those in the acute group. However, after 1 day of treatment, there was no difference in VAS between the two groups. None of the patients in the acute phase treated with BoNT-A developed PHN. BoNT-A injections significantly reduced herpetic-related pain and proved to be a more effective treatment for the PHN versus acute pain group. Moreover, an early application of BoNT-A can alleviate the probability of developing PHN.

Intradermal miR-16–5p targets Akt3 and reduces RTX-induced postherpetic neuralgia-mimic pain in mice

The molecular mechanisms of refractory pain in postherpetic neuralgia (PHN) patients are not fully understood. PHN may be related to skin abnormality after herpes zoster induced skin lesions. We previously reported 317 differentially expressed microRNAs (miRNAs) in PHN skin compared with the contralateral normal mirror skin. In this study, 19 differential miRNAs were selected and the expression was validated in other 12 PHN patients. The expression levels of miR-16–5p, miR-20a-5p, miR-505–5p, miR-3664–3p, miR-4714–3p and let-7a-5p are lower in PHN skin, which is the same as those in microarray experiment. To evaluate the effects of cutaneous miRNA on PHN, the expression of candidate miRNAs is further observed in resiniferatoxin (RTX) induced PHN-mimic mice model. In the plantar skin of RTX mice, miR-16–5p and let-7a-5p are downregulated, with the same expression trend of PHN patients. In addition, intraplantar injection of agomir-16–5p reduced mechanical hyperalgesia, and improved thermal hypoalgesia in RTX mice. Furthermore, agomir-16–5p down-regulated the expression levels of Akt3, which is the target gene of agomir-16–5p. These results suggest that intraplantar miR-16–5p may alleviate RTX induced PHN-mimic pain by inhibiting the expression of Akt3 in the skin.

Analysis of the efficacy and safety of CT-guided radiofrequency ablation of posterior root of the spinal nerve in the treatment of postherpetic neuralgia

Objective: To investigate the efficacy and safety of CT-guided radiofrequency ablation of posterior root of spinal nerve in the treatment of postherpetic neuralgia (PHN). Methods: A total of 102 PHN patients (42 males and 60 females) aged (69.7±9.4) years who underwent CT-guided radiofrequency ablation of posterior root of spinal nerve in the Department of Pain Medicine of the Affiliated Hospital of Jiaxing University from January 2017 to April 2020 were retrospectively included. Patients were followed up, and numerical rating scale (NRS) score, Pittsburgh sleep quality index (PSQI), satisfaction score and complications before surgery (T0) and at 1 d (T1), 3 months (T2), 6 months (T3), 9 months (T4) and 12 months (T5) after surgery were recorded. Results: The NRS score of PHN patients at T0, T1, T2, T3, T4, and T5 [M(Q1, Q3)] was 6(6, 7), 2(2, 3), 3(2, 4), 3(2, 4), 2(1, 4), 2(1, 4), respectively. Likewise, the PSQI score [M(Q1, Q3)] at aforementioned time points was 14(13, 16), 4(3, 6), 6(4, 8), 5(4, 6), 4(2, 8), 4(2, 9), respectively. Compared with T0, the NRS and PSQI scores at all time points from T1 to T5 were lower, with statistically significant differences (all P<0.001). The overall effective rate of surgery at 1 year postoperatively was 71.6% (73/102) with a satisfaction score of 8(5, 9), and the recurrence rate was 14.7% (15/102) with a recurrence time of (7.5±0.8) months. The main postoperative complication was numbness, with an incidence of 86.0% (88/102), and the degree of numbness gradually decreased with time. Conclusion: CT-guided radiofrequency ablation of posterior root of spinal nerve for PHN has a high effective rate and a low recurrence rate, with high safety profile, and may be a feasible surgical option for the treatment of PHN.

Bibliometric analysis of research articles on post-herpetic neuralgia published from 1991 to 2020.

Post-herpetic neuralgia (PHN) is one of the most painful diseases, which has made it a major concern for pain physicians. We aimed to quantitatively analyze the research outputs of studies on PHN published over the past 30 years using bibliometric analysis. We also aimed to analyze the research outputs of studies on interventional treatments for PHN and evaluate the academic achievements of Korean pain physicians. Bibliometric analysis was performed by searching the Web of Science database for PHN-related articles published between 1991 and 2020. Publication number, year, source, country, institution, and citation-related information were retrieved from the database. We also quantitatively analyzed publications related to interventional treatments for PHN. A total of 3285 publications were extracted from the database; 101 (3.1%) of the articles were published by South Korean authors, making South Korea the 11th in the order of countries that published the most articles. There were 185 articles on the effects of interventional treatments for PHN. South Korean authors published 30 (16.2%) articles out of these, making South Korea the 3rd in the order of countries that published the most articles on the effects of interventional treatment for PHN. Our results showed an increasing trend in the number of PHN-related publications and the academic achievements of Korean pain physicians in this field over the past 3 decades. However, the proportion of studies on interventional treatments is relatively small. Korean pain physicians need to establish academic evidence on interventional treatment to expand their role in this field and improve the outcomes of PHN patients.

Genetic polymorphisms of PRKAA1 (AMPKα1) and postherpetic pain susceptibility: Multicenter, randomized control, and haplotype analysis study.

Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is a pivotal regulatory protein in energy metabolism. In a pilot study, we found that AMPK-associated energy metabolism imbalance in neurons contributes to the occurrence and maintenance of neuropathic pain (NeP). This study aimed to explore the relationship between genetic polymorphisms of AMPK gene (Rs13361707, rs3792822, and rs10074991) in PRKAA1 and postherpetic neuralgia (PHN) in Chinese individuals. Hundred and thirty two patients with PHN and 118 control individuals were enrolled in this study. All blood samples were shuffled and blinded to the person performing the haplotype analysis. Rs13361707, rs3792822, and rs10074991 PRKAA1 genotypes were identified in all participants. Dominant and recessive models were used for evaluating the association between these nucleotide polymorphisms and PHN susceptibility. A haplotype analysis of PHN patients and healthy controls was performed. Clinical characteristics between the two groups were not significantly different (p > 0.05) except that the ages in control subjects were younger than the PHN patients (p < 0.05). Genotypes and allele frequencies are significantly different between the PHN patients and control subjects for the rs13361707 and rs10074991 polymorphisms (p < 0.05), but not for rs3792822 (p > 0.05). In addition, the CCG haplotype of rs13361707-rs3792822-rs10074991 correlated negatively with PHN occurrence, but TCA was positively correlated with PHN (p < 0.05). Our results indicate that PRKAA1 gene polymorphisms rs13361707 and rs10074991 were associated with a risk of PHN, and that the CCG haplotype of rs13361707-rs3792822-rs10074991 correlated negatively with PHN occurrence in haplotype analysis. TCA was positively associated with PHN in Chinese individuals.

Stability of High Concentration Capsaicin in Transfersome Carriers in Gel Dosage Form

Topical capsaicin with high concentrations (8%) is effective in the treatment of pain in Post-Herpetic Neuralgia (PHN) and HIV-Associated Distal Sensory Polyneuropathy (HIV-DSP) patients. High concentrations of capsaicin encapsulated in transfersome nanovesicles aim to reduce the irritating ability of capsaicin when using as drugs. Gel preparations were chosen in the formulation because they are non-sticky, easy to wash, easy to apply, and more practical. The components contained in the gel affect the stability of the gel. Physical and chemical stability tests need to be carried out to ensure the quality, safety and efficacy of the gel so that it meets the expected specifications during its shelf life. This study aims to determine the stability of selected gel formulas containing high concentrations of transfersome capsaicin. The selected gel formula is a gel containing a mixture of phosphatidylcholine (Phospholiphon 90G®) and Tween 80 (80:20). Stability was carried out at high temperature (40±2oC), room temperature (30±2oC), low temperature (5±3oC), and cycling test. The stability parameters tested included organoleptic, pH, viscosity, and assay. The results of the transfersom capsaicin gel stability test showed no change in pH, viscosity, and assay in all storage conditions, but the gel showed a change in color, smell, and taste when stored at high temperatures (40 ± 2oC). It can be concluded that the resulting capsaicin transfersome gel formula with a phospholipid:tween ratio of 80 (80:20) was less stable during 12 weeks of storage at 40 oC