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Objective: Available treatment for chronic neuropathic pain is still limited, and the positive effects are modest. Thus, clinicians aim to improve activity and quality of life despite pain. The objective monitoring of activity is attracting attention in chronic pain assessments. Therefore, we objectively evaluated daytime activity and sleep in patients with postherpetic neuralgia (PHN), using actigraphy to determine risk factors for decreased activity., Methods: Participants with PHN wore an actigraph (a wristwatch-like accelerometer) on the nondominant hand. The actigraph measured day-time activity and sleep, which were compared with participant-reported subjective pain and sleep assessments., Results: Fifty-four individuals with PHN who visited our outpatient clinic completed questionnaires and a week of actigraph monitoring. Subjective scores of pain intensity, neuropathic pain, disability in daily life, pain-catastrophizing thoughts, and insomnia were all well correlated. However, the actigraph-monitored activity levels, using 2 equations, and sleep quality were not associated with any pain or sleep-related subjective scores., Conclusion: The discrepancy between the subjective and objective scores in this study may be due to (1) features of PHN, an archetype of peripheral neuropathic pain affecting no motor nerves, (2) actigraph measurement limitations regarding the sedentary life of the elderly, or (3) activity misperception, a new proposition explaining the discrepancy between subjective and objective measures of activity, similar to the sleep state misperception. In patients with PHN, high pain intensity may be reported in those with highly maintained activity, in which treatment must be selected cautiously to prevent interruption of their physical abilities., Competing Interests: This study was supported by a Grant-in-Aid. JSPS KAKENHI, Kojimachi, Chiyoda-ku, Tokyo, Japan, Grant Number 22K09018. The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Background: Postherpetic neuralgia (PHN) is a classic chronic condition with multiple signs of peripheral and central neuropathy. Unfortunately, the pathogenesis of PHN is not well defined, limiting clinical treatment and disease management., Objective: To describe the peripheral and central pathological axes of PHN, including peripheral nerve injury, inflammation induction, central nervous system sensitization, and brain functional and structural network activity., Methods: A bibliographic survey was carried out, selecting relevant articles that evaluated the characterization of the pathogenesis of PHN, including peripheral and central pathological axes., Results: Currently, due to the complexity of the pathophysiological mechanisms of PHN and the incomplete understanding of the exact mechanism of neuralgia., Conclusion: It is essential to conduct in-depth research to clarify the origins of PHN pathogenesis and explore effective and comprehensive therapies for PHN., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

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., (© 2021. The Author(s).)

The brain and the spinal cord together make up the central nervous system (CNS). The functions of the human brain have been the focus of neuroscience research for a long time. However, the spinal cord is largely ignored, and the functional interaction of these two parts of the CNS is only partly understood. This study developed a novel method to simultaneously record spinal cord electrophysiology (SCE) and electroencephalography (EEG) signals and validated its performance using a classical resting-state study design with two experimental conditions: eyes-closed (EC) and eyes-open (EO). We recruited nine postherpetic neuralgia patients implanted with a spinal cord stimulator, which was modified to record SCE signals simultaneously with EEG signals. For both EEG and SCE, similar differences were found in delta- and alpha-band oscillations between the EC and EO conditions, and the spectral power of these frequency bands was able to predict EC/EO behaviors. Moreover, causal connectivity analysis suggested a top-down regulation in delta-band oscillations from the brain to the spinal cord. Altogether, this study demonstrates the validity of simultaneous SCE-EEG recording and shows that the novel method is a valuable tool to investigate the brain-spinal interaction. With this method, we can better unite knowledge about the brain and the spinal cord for a deeper understanding of the functions of the whole CNS., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2021. Published by Elsevier Inc.)

Purpose of Review: Chest pain is a very common presenting complaint among patients in the hospital, a large proportion of whom have non-cardiac chest pain (NCCP). Neurological causes of NCCP have not been previously reviewed although several causes have been identified., Recent Findings: Chest pain has been reported as a symptom of multiple neurological conditions such as migraine, epilepsy, and multiple sclerosis, with varying clinical presentations. The affected patients are often not formally diagnosed for long periods of time due to difficulties in recognizing the symptoms as part of neurological disease processes. This paper will briefly summarize well-known etiologies of chest pain and, then, review neurological causes of NCCP, providing an overview of current literature and possible pathophysiologic mechanisms.

In recent decades, an increasing number of neuroimaging studies utilizing magnetic resonance imaging (MRI) have explored the differential effects of postherpetic neuralgia (PHN) on brain structure and function. We systematically reviewed and integrated the findings from relevant neuroimaging studies in PHN patients. A total of 15 studies with 16 datasets were ultimately included in the present study, which were categorized by the different neuroimaging modalities. The results revealed that PHN was closely associated with structural/microstructural and functional abnormalities of the brain mainly located in the 'pain matrix', including the thalamus, insula, parahippocampus, amygdala, dorsolateral prefrontal cortex, precentral gyrus and inferior parietal lobe, as well as other regions, such as the precuneus, lentiform nucleus and brainstem. Furthermore, a disruption of multiple networks, including the default-mode network, salience network and limbic system, may contribute to the neurophysiological mechanisms underlying PHN. The findings indicate that the cerebral abnormalities of PHN were not restricted to the pain matrix but extended to other regions, profoundly affecting the regulation and moderation of pain processing in PHN. Future prospective and longitudinal neuroimaging studies with larger samples will elucidate the progressive trajectory of neural changes in the pathophysiological process of PHN., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Herpes zoster (HZ), is a painful skin rash disease with cutaneous symptoms and acute zoster-associated pain (ZAP). Postherpetic neuralgia (PHN), as the most frequent sequela of HZ, can persist a long time. Both HZ and PHN may significantly impact the quality of life and made great economical afford to affected patients. Its optimal treatment on HZ and PHN is still an urgent problem. In China, thermotherapy, including moxibustion and fire needle, is widely used because they can quickly promote the recovery of shingles and reduce the occurrence of PHN. Thermotherapy can also reduce pain intensity, relieve anxiety, and improve quality of life of PHN. Based on the current literatures, the effect and safety of thermotherapy will be systematically evaluated to provide appropriate complementary therapies for HZ and PHN., Methods: Studies search for eligible randomized controlled trials (RCTs) that use thermotherapy including fire needle and moxibustion for HZ or PHN from the following databases: PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine Database (CBM), Technology Periodical database (VIP), and Wanfang database. Language restrictions for retrieving literature are English and Chinese. Their data extraction will be done by 2 researchers. Mean difference (MD) or relative risk (RR) with fixed or random effect model in terms of 95% confidence interval (CI) will be adopted for the data synthesis. To evaluate the risk of bias, the Cochrane's risk of bias assessment tool will be utilized. The sensitivity or subgroup analysis will also be conducted when meeting high heterogeneity (I2 > 50%)., Results: This meta-analysis will provide an authentic synthesis of the thermotherapy's effect on HZ and PHN, including incidence of postherpetic neuralgia and adverse events., Discussion: The findings of the review offer updated evidence and identify whether thermotherapy can be an effective treatment for HZ and PHN for clinicians., Registration Number: INPLASY2020110009., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Previous studies of herpes zoster (HZ) have focused on acute patient manifestations and the most common sequela, postherpetic neuralgia (PHN), both serving to disrupt brain dynamics. Although the majority of such patients gradually recover, without lingering severe pain, little is known about life situations of those who recuperate or the brain dynamics. Our goal was to determine whether default mode network (DMN) dynamics of the recuperative population normalize to the level of healthy individuals., Methods: For this purpose, we conducted resting-state functional magnetic resonance imaging (fMRI) studies in 30 patients recuperating from HZ (RHZ group) and 30 healthy controls (HC group). Independent component analysis (ICA) was initially undertaken in both groups to extract DMN components. DMN spatial maps and within-DMN functional connectivity were then compared by group and then correlated with clinical variables., Results: Relative to controls, DMN spatial maps of recuperating patients showed higher connectivity in middle frontal gyrus (MFG), right/left medial temporal regions of cortex (RMTC/LMTC), right parietal lobe, and parahippocampal gyrus. The RHZ (vs HC) group also demonstrated significant augmentation of within-DMN connectivity, including that of LMTC-MFG and LMTC-posterior cingulate cortex (PCC). Furthermore, the intensity of LMTC-MFG connectivity correlated significantly with scoring of pain-induced emotions and life quality., Conclusion: Findings of this preliminary study indicate that a disrupted dissociative pattern of DMN persists in patients recuperating from HZ, relative to healthy controls. We have thus provisionally established the brain mechanisms accounting for major outcomes of HZ, offering heuristic cues for future research on HZ transition states., (© 2020 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Postherpetic Neuralgia (PHN), develops after the resolution of the herpes zoster mucocutaneous eruption, is a debilitating chronic pain. However, there is a lack of knowledge regarding the underlying mechanisms associated with ascending and descending pain modulations in PHN patients. Here, we combined psychophysics with structural and functional magnetic resonance imaging (MRI) techniques to investigate the brain alternations in PHN patients. Psychophysical tests showed that compared with healthy controls, PHN patients had increased state and trait anxiety and depression. Structural MRI data indicated that PHN patients had significantly smaller gray matter volumes of the thalamus and amygdala than healthy controls, and the thalamus volume was negatively correlated with pain intensity (assessed using the Short-form of the McGill pain questionnaire) in PHN patients. When the thalamus and periaqueductal gray matter (PAG) were used as the seeds, resting-state functional MRI data revealed abnormal patterns of functional connectivity within ascending and descending pain pathways in PHN patients, e.g., increased functional connectivity between the thalamus and somatosensory cortices and decreased functional connectivity between the PAG and frontal cortices. In addition, subjective ratings of both Present Pain Index (PPI) and Beck-Depression Inventory (BDI) were negatively correlated with the strength of functional connectivity between the PAG and primary somatosensory cortex (SI), and importantly, the effect of BDI on PPI was mediated by the PAG-SI functional connectivity. Overall, our results provided evidence suggesting deficits in ascending and descending pain modulation pathways, which were highly associated with the intensity of chronic pain and its emotional comorbidities in PHN patients. Therefore, our study deepened our understanding of the pathogenesis of PHN, which would be helpful in determining the optimized treatment for the patients., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To explore the brain microstructural and functional changes in patients with postherpetic neuralgia (PHN)., Materials and Methods: 12 PHN patients and 12 healthy volunteers were enrolled. Diffusion tensor imaging (DTI) and resting-state functional MRI (rfMRI) sequences were scanned by a 3T MR scanner. Fractional anisotropy (FA) and mean diffusivity (MD) t-maps were obtained following DTI data processing. The amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were obtained following rfMRI data processing. A two sample t-test was performed to compare the FA, MD, ALFF and fALFF differences between the PHN patients and healthy controls., Results: No significant differences were noted with regard to the parameters gender, age and education years between the two groups. FA, MD, ALFF and/or fALFF indicated significant alterations in specific pain or pain-related brain regions, such as brainstem, cerebellum, parietal lobe, precuneus, frontal lobe, temporal lobe, postcentral and precentral gyrus, corpus callosum, cingulate gyrus, putamen and insula., Conclusion: Multi-local alterations of spontaneous brain activity could form a network related to chronic pain, sensory discrimination, emotion and cognition, suggesting complicated central mechanisms of PHN. The combined-action of brain microstructure and function may play a critical role in comprehension of neurological mechanisms of PHN-induced pain.

Established conventional treatments for postherpetic neuralgia (PHN) and postherpetic itch (PHI) are difficult and often disappointing. In this study, the authors investigated the effect and mechanisms of extracorporeal shockwave therapy (ESWT) on pain and itch associated with PHN and PHI.Thirteen patients, 50 to 80 years of age, with symptoms associated with PHN or PHI (duration of persistent pain >3 months) and complaints of pain or itch rated >4 on a numerical rating scale (NRS), were included. ESWT was administered using a shockwave device (Piezo Shockwave, Richard Wolf GmbH, Knittlingen, Germany) to skin areas affected by pain or itch. An energy flux density of 0.09 to 0.16 mJ/mm at a frequency of 5 Hz and 2000 impulses was administered at 3-day intervals for 6 sessions. The NRS, 5D-Itch Scale, and Patients Global Impression of Change (PGIC) scale were used to evaluate the efficacy of ESWT.NRS scores of pain and itch and 5D-Itch Scale scores decreased significantly compared with before treatment and at the end of the treatment sessions (P < .0001, P = .001, P = .0002, respectively). There was a statistically significant difference between PGIC scores, which were checked every 2 sessions (P < .0001).ESWT is a noninvasive modality that significantly reduced PHN-associated pain and itch.

Our objective was to develop comprehensive national estimates of the total burden of herpes zoster (HZ) among U.S. adults, including direct (ie, medical costs) and indirect (ie, productivity losses) costs, as well as its psychosocial impact (ie, quality of life losses). Using a patient-level microsimulation model, we projected health and economic outcomes among U.S. adults aged 18 years and older using a 10-year time horizon. We conducted a comprehensive systematic literature review to generate parameter values and conducted simulation modeling to generate our outcomes, including numbers of cases of uncomplicated HZ, postherpetic neuralgia (PHN), and ocular complications, productivity losses, and losses in quality-adjusted life years (QALYs). We used a societal perspective for outcomes; the costing year was 2015. Projected outcomes for an unvaccinated population included 1.1 million HZ cases, 114,000 PHN cases, and 43,000 ocular complications annually, resulting in approximately 67,000 QALYs lost. HZ and its complications would incur costs of $2.4 billion in direct medical costs and productivity losses annually. Projected QALY losses were most sensitive to HZ and PHN health utility values in the model. Cost estimates were most sensitive to the probability of HZ and to the costs per episode of PHN. The national burden of direct, indirect, and psychosocial HZ costs is substantial. Our results can inform economic analyses for HZ vaccines. Comprehensive, national assessments of the total burden of other painful conditions would be very informative.

Postherpetic neuralgia (PHN) is the most common complication of shingles caused by reactivation of varicella zoster virus (VZV). Management of PHN is often suboptimal while using current conventional treatments. Antiviral therapy was used to reduce PHN-associated pain in two small trials which showed conflicting results. We hypothesize the analgesic efficacy of antiviral therapy on PHN is affected by patient characteristics including pathophysiology of the participants and serum vitamin D levels. Pathophysiology of PHN includes neuronal excitability and chronic VZV ganglionitis (persistent active VZV infection in ganglions). VZV-DNA positivity or a positive IgG coupled with a positive IgM indicates recent or current VZV infection. Positive VZV-DNA or IgG/IgM tests are used to confirm whether the patients experience chronic VZV ganglionitis. Antiviral therapy decreases pain in PHN patients with chronic VZV ganglionitis; whereas, antiviral therapy shows no effects in PHN patients with negative VZV-DNA or IgM. Vitamin D is a natural antiviral mediator. Studies show a high prevalence of vitamin D deficiency in hepatitis B/C virus-infected patients. Serum vitamin D levels and vitamin D supplementation are factors which affect the antiviral efficacy on hepatitis B/C virus infection. Serum 25-OHD levels of hospitalized patients with shingles were significantly lower compared to healthy controls. Accordingly, PHN patient may have a high prevalence of vitamin D deficiency which negatively affects the antiviral efficacy. Vitamin D supplementation may improve the antiviral efficacy on PHN. Future trials regarding antiviral therapy on PHN should consider patient characteristics and should be conducted among different subgroups of PHN patients., (Copyright © 2019. Published by Elsevier Ltd.)

The effects of repetitive transcranial magnetic stimulation (rTMS), the clinical treatment for postherpetic neuralgia (PHN), on whole-brain functional network of PHN patients is not fully understood.To explore the effects of rTMS on the whole-brain functional network of PHN patients.10 PHN patients (male/female: 5/5 Age: 63-79 years old) who received rTMS treatment were recruited in this study. High-resolution T1-weighted and functional Magnetic Resonance Imaging (fMRI) were acquired before and after 10 consecutive rTMS sessions. The whole-brain functional connectivity networks were constructed by Pearson correlation. Global and node-level network parameters, which can reflect the topological organization of the brain network, were calculated to investigate the characteristics of whole-brain functional networks. Non-parametric paired signed rank tests were performed for the above network parameters with sex and age as covariates. P < .05 (with FDR correction for multi-comparison analysis) indicated a statistically significant difference. Correlation analysis was performed between the network parameters and clinical variables.The rTMS showed significant increase in characteristic path length and decrease of clustering coefficient, global, and local efficiency derived from the networks at some specific network sparsity, but it showed no significant difference for small-worldness. rTMS treatment showed significant differences in the brain regions related to sensory-motor, emotion, cognition, affection, and memory, as observed by changes in node degree, node betweenness, and node efficiency. Besides, node-level network parameters in some brain areas showed significant correlations with clinical variables including visual analog scales (VAS) and pain duration.rTMS has significant effects on the whole-brain functional network of PHN patients with a potential for suppression of sensory-motor function and improvement of emotion, cognition, affection, and memory functions.

This prospective cohort study aimed to characterize the sensory profile during acute herpes zoster (AHZ) and to explore sensory signs as well as physical and psychosocial health as predictors for postherpetic neuralgia (PHN). Results of quantitative sensory testing of 74 patients with AHZ at the affected site and at the distant contralateral control site were compared to a healthy control group. Pain characteristics (Neuropathic Pain and Symptom Inventory and SES), physical functioning, and psychosocial health aspects (Pain Disability Index, SF-36, and STAI) were assessed by questionnaires. Patients with PHN (n = 13) at 6-month follow-up were compared to those without PHN (n = 45). Sensory signs at the affected site were thermal and vibratory hypesthesia, dynamic mechanical allodynia (DMA), pressure hyperalgesia, and high wind-up (18%-29%), as well as paradoxical heat sensations and pinprick hypalgesia (13.5%). The unaffected control site exhibited thermal and vibratory hypesthesia, DMA, and pressure hyperalgesia. Dynamic mechanical allodynia and pinprick hypalgesia were mutually exclusive. Postherpetic neuralgia was associated with DMA (38.5% vs 6.7%; P = 0.010) and vibratory hypesthesia (38.5% vs 11.1%; P = 0.036) at the control site, with mechanical gain and/or loss combined with normal thermal detection (affected site: 69.2% vs 31.1%; P = 0.023; control site: 53.8% vs 15.5%; P = 0.009). Pain Disability Index (P = 0.036) and SES affective pain perception scores (P = 0.031) were over 50% higher, and 6 of 8 SF-36 subscores were over 50% lower (P < 0.045) in PHN. Sensory profiles in AHZ indicate deafferentation and central but not peripheral sensitization. Sensory signs at distant body sites, strong affective pain perception, as well as reduced quality of life and physical functioning in the acute phase may reflect risk factors for the transition to PHN.

Postherpetic itch (PHI), or herpes zoster itch, is an intractable and poorly understood disease. We targeted 94 herpes zoster patients to investigate their pain and itch intensities at three separate stages of the condition (acute, subacute, and chronic). We used painDETECT questionnaire (PDQ) scores to investigate the correlation between PHI and neuropathic pain. Seventy-six patients were able to complete follow-up surveys. The prevalence of PHI was 47/76 (62%), 28/76 (37%), and 34/76 (45%) at the acute, subacute, and chronic stages, respectively. PHI manifestation times and patterns varied. We investigated the relationship of PHI with neuropathic pain using the visual analog scale (VAS), which is a measure of pain intensity, and the PDQ, which is a questionnaire used to evaluate the elements of neuropathic pain. The VAS and PDQ scores did not differ significantly between PHI-positive and PHI-negative patients. A large neuropathic component was not found for herpes zoster itch, suggesting that neuropathic pain treatments may not able to adequately control the itch. Accordingly, we suggest that a more PHI-focused therapy is required to address this condition.

Introduction: The aim of this study was to explore a method for obtaining sensory nerve action potentials (SNAPs) of the supratrochlear (STN) and supraorbital (SON) nerves and evaluate the function of affected nerves in patients with herpetic ophthalmic neuralgia (HON)., Methods: Thirty healthy volunteers and 40 subjects with subacute HON participated in this study., Results: The amplitudes and sensory conduction velocities (SCVs) that predicted HON were identified. The corresponding cutoff values for the amplitudes ranged from 11.10 μV to 12.45 μV. The corresponding cutoff values for the SCVs ranged from 43.14 m/s to 44.64 m/s. SCVs were markedly lower on the affected side compared with healthy volunteers (P < 0.05), and the amplitudes of SNAPs on the affected side were decreased by 36% compared with healthy volunteers (P < 0.05)., Discussion: SCVs of STN and SONs can be obtained with the 3-channel method and used to evaluate myelinated fibers in patients with HON. Muscle Nerve 57: 973-980, 2018., (© 2018 Wiley Periodicals, Inc.)

Background: ZOSTAVAX (ZVL; Zoster Virus Live), is a single dose, live, attenuated vaccine licensed for the prevention of herpes zoster (HZ) and post herpetic neuralgia (PHN) in adults ≥50 years of age. Injection site adverse events (AEs) of erythema, swelling and pain were solicited within 5 days post vaccination in the 2 pivotal studies of ZVL; ZEST (ZOSTAVAX Efficacy and Safety Trial) and SPS (Shingles Prevention Study). Protocol specified criteria were used to report the frequency and intensity of injection site AEs in ZEST and SPS studies. Subsequently, the FDA Toxicity Grading Scale provided guidance for uniform assessment of AEs across all adult vaccine clinical trials. The objective of this post-hoc analysis was to categorize the previously reported injection site AEs in two pivotal trials of ZVL according to the current FDA Toxicity Grading Scale., Methods: The current FDA Toxicity Grading Scale provides a measure for classifying injection site AEs by four grades [Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe) and Grade 4 (life threatening)]. Injection site erythema, swelling, and pain intensity gradings were assigned to the respective FDA Toxicity Grade based on this appropriation. A descriptive analysis of the proportion and risk difference (within 95% confidence intervals) of injection site AEs per the FDA Toxicity Grading Scale is provided., Results: The frequency of injection site AEs (erythema, swelling, pain) after subcutaneous vaccination with ZVL were higher in recipients of ZVL compared with placebo. Majority of the injection site AEs observed were Grade 1 (mild) or Grade 2 (moderate) in intensity. Additionally, Grade 3 (severe) injection site AEs were observed infrequently., Conclusions: Application of the FDA Toxicity Grading Scale provides a uniform AE assessment tool across different adult vaccines. This post hoc summary of injection site AEs using FDA Toxicity Grading Scale provides further evidence of low frequency of severe injection site AEs post ZVL vaccination.

Introduction: Varicella Zoster Virus (VZV) is associated with many disorders of the central and peripheral nervous systems including neuralgia, meningitis, meningoencephalitis, cerebellitis, vasculopathy, myelopathy, Ramsay-Hunt syndrome, and polyneuritis cranialis. Cranial nerves V, VI, VII, VIII, IX, X, XI, and/or XII may be affected. The neurological disorders caused by VZV usually present with rash, but may rarely present without rash., Case Report: We herein present a case of polyneuritis cranialis without rash caused by VZV affecting cranial nerves VII, VIII, IX, and X. After excluding other causes of the condition, we diagnosed VZV infection based on VZV DNA in the CSF and an elevated anti-VZV IgG level in serum. The patient responded well to antiviral therapy., Conclusion: VZV infection should be kept in mind during the differential diagnosis of polyneuritis cranialis; it is important to note that VZV re-activation may occur without rash.

Background: Herpes zoster (HZ) can develop into postherpetic neuralgia (PHN), both of which are painful diseases. PHN patients suffer chronic pain and emotional disorders. Previous studies showed that the PHN brain displayed abnormal activity and structural change, but the difference in brain activity between HZ and PHN is still not known., Objectives: To identify regional brain activity changes in HZ and PHN brains with resting-state functional magnetic resonance imaging (rs-fMRI) technique, and to observe the differences between HZ and PHN patients., Study Design: Observational study., Setting: University hospital., Methods: Regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) methods were employed to analysis resting-state brain activity. Seventy-three age and gender matched patients (50 HZ, 23 PHN) and 55 healthy controls were enrolled. ReHo and fALFF changes were analyzed to detect the functional abnormality in HZ and PHN brains., Results: Compared with healthy controls, HZ and PHN patients exhibited abnormal ReHo and fALFF values in classic pain-related brain regions (such as the frontal lobe, thalamus, insular, and cerebellum) as well as the brainstem, limbic lobe, and temporal lobe. When HZ developed to PHN, the activity in the vast area of the cerebellum significantly increased while that of some regions in the occipital lobe, temporal lobe, parietal lobe, and limbic lobe showed an apparent decrease., Limitations: (a) Relatively short pain duration (mean 12.2 months) and small sample size (n = 23) for PHN group. (b) Comparisons at different time points (with paired t-tests) for each patient may minimize individual differences., Conclusions: HZ and PHN induced local brain activity changed in the pain matrix, brainstem, and limbic system. HZ chronification induced functional change in the cerebellum, occipital lobe, temporal lobe, parietal lobe, and limbic lobe. These brain activity changes may be correlated with HZ-PHN transition., Key Words: Herpes zoster, postherpetic neuralgia, resting-state fMRI (rs-fMRI), regional homogeneity (ReHo), fractional aptitude of low-frequency fluctuation (fALFF).

Background: Post-herpetic neuralgia (PHN), which develops after the resolution of a herpes zoster eruption, is an exceptionally drug-resistant neuropathic pain. The unsatisfactory management of PHN partly results from the difficulty in dissecting out its contributing factors due to the complexity of PHN mechanism., Methods: Here, to elaborate our understanding of the PHN mechanism and to establish a basis for effective therapeutic strategies, we comprehensively investigated the contributions of multiple factors to PHN severity., Results: Based on the comparison of somatosensory detection thresholds (C, Aδ and Aβ fibre thresholds) between affected and unaffected sides, 16 PHN patients with significant sensory deficits and 13 PHN patients without significant sensory deficits were identified and assigned to different groups. The different extents of lesions in the nociceptive system between patients with and without sensory deficits were confirmed using laser-evoked brain responses. Moreover, patients with sensory deficits had more severe pain and psychological disorders, e.g. anxiety and depression. Importantly, chronic pain severity was significantly influenced by various psychophysiological factors (sleep disturbances, psychological disorders and hypothalamic-pituitary-adrenal axis dysfunction) for patients with sensory deficits., Conclusions: Our findings demonstrated the contribution of multiple patho-psychophysiological factors to PHN severity, which could help establish a basis for the development of a rational, patient-centred therapeutic strategy., Significance: This study revealed the contribution of multiple patho-psychophysiological factors to PHN severity, which expanded our understanding of the underlying PHN mechanism, and helped develop a rational, patient-centred therapeutic strategy targeting towards the corresponding etiology and psychophysiological disorders for individual patient., (© 2016 European Pain Federation - EFIC®.)

Background: Postherpetic neuralgia (PHN) patients suffer debilitating chronic pain, hyperalgesia, and allodynia, as well as emotional disorders such as insomnia, anxiety, and depression. The brain structure and functional basis of PHN are still not fully understood., Objectives: To identify the changes of regional brain activity in resting-state PHN patients using regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) methods. Correlations between spontaneous pain intensity and ReHo or fALFF were analyzed., Study Design: Observational study., Setting: University hospital., Methods: ReHo, fALFF change was analyzed in 19 PHN patients and 19 healthy controls to detect the functional abnormality in the brains of PHN patients. Correlations between ReHo, fALFF, and PHN pain intensity were assessed in the PHN group., Results: PHN patients exhibited significantly abnormal ReHo and fALFF intensity in several brain regions, including the brainstem, thalamus, limbic system, temporal lobe, prefrontal lobe, and cerebellum compared with healthy controls. Correlation analysis showed that most of the ReHo values of the aforementioned brain regions positively correlated with visual analog scale (VAS) values. But much less correlation was found between fALFF and VAS., Limitations: (a) No specific emotional assessment was given for PHN patients before fMRI scans, therefore we cannot exclude whether the emotional disorders exist in these patients. (b) Relatively short pain duration (mean 5.4 months) and small sample size (n = 19) for the PHN group., Conclusions: For PHN patients, the local brain activity abnormality was not restricted to the pain matrix. Besides regions related to pain perception, areas in charge of affective processes, emotional activity, and pain modulation also showed abnormal local brain activity in a resting state, which may suggest complicated supraspinal function and plasticity change in PHN patients. ReHo was more closely correlated with pain intensity of PHN patients than fALFF. This work indicates that besides physical and emotional pain perception, mood disorder and pain modulation could be characteristic of PHN patients. This also supports the potential use of therapeutic interventions not only restricted to pain alleviation, but that also attempt to ameliorate the cognitive and emotional comorbidities. Key words: Postherpetic neuralgia, resting-state fMRI (rs-fMRI), mood disorder, limbic system, fractional aptitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo).

Background: Postherpetic neuralgia (PHN) is a chronic neuropathic pain that results from alterations of the peripheral nervous system in areas affected by the herpes zoster virus. The symptoms include pain, paresthesia, dysesthesia, hyperalgesia, and allodynia. Despite the availability of pharmacological treatments to control these symptoms, no treatments are available to control the underlying pathophysiology responsible for this disabling condition., Methods/design: Patients with herpes zoster who are at least 50 years old and have a pain score of 4 or higher on a visual analogue scale (VAS) will be recruited. The aim is to recruit 134 patients from the practices of general physicians. Participants will be randomized to receive gabapentin to a maximum of 1800 mg/day for 5 weeks or placebo. Both arms will receive 1000-mg caplets of valacyclovir three times daily for 7 days (initiated within 72 h of the onset of symptoms) and analgesics as needed. The primary outcome measure is the percentage of patients with a VAS pain score of 0 at 12 weeks from rash onset. The secondary outcomes measures are changes in quality of life (measured by the SF-12 questionnaire), sleep disturbance (measured by the Medical Outcomes Study Sleep Scale), and percentage of patients with neuropathic pain (measured by the Douleur Neuropathique in 4 Questions)., Discussion: Gabapentin is an anticonvulsant type of analgesic that could prevent the onset of PHN by its antihypersensitivity action in dorsal horn neurons., Trial Registration: ISRCTN Registry identifier: ISRCTN79871784 . Registered on 2 May 2013.

Objective . PainVision device was a developed application for the evaluation of pain intensity. The objective was to assess the efficacy and safety of pulsed radiofrequency (PRF) combined with pharmacological therapy in the treatment of postherpetic neuralgia (PHN). We also discussed the correlation of the measurements. Method . Forty patients with PHN were randomized for treatment with PRF combined with pharmacological therapy (PRF group, n = 20) or pharmacological therapy (control group, n = 20) at postoperative 48 hours. The efficacy measure was pain degree (PD) that was assessed by PainVision and visual analog scale (VAS), short form Mcgill pain questionnaire (SF-Mcgill), and numeric rate scale sleep interference score (NRSSIS). Correlations between PD, VAS, SF-Mcgill, and NRSSIS were determined. Results . The PD for persistent pain (PP) and breakthrough pain (BTP) at postoperative 48 hours assessed by PainVision were significantly lower in PRF group than in control group (PD-PP, P < 0.01; PD-BTP, P < 0.01). PD and VAS were highly correlated for both persistent pain ( r = 0.453, ρ = 0.008) and breakthrough pain ( r = 0.64, ρ = 0.001). Conclusion . PRF was well tolerated and superior to isolated pharmacological therapy in the treatment of PHN. PainVision device showed great value in the evaluation of pain intensity and PD had an excellent correlation with VAS and SF-Mcgill., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Post-herpetic neuralgia (PHN) is a chronic neuropathic pain condition that persists 3 months or more following an outbreak of shingles. Shingles, also known as acute herpes zoster, is associated with the reactivation of the dormant varicella zoster virus in an individual who has experienced chicken pox. PHN is associated with persistent and often refractory neuropathic pain. Patients may experience multiple types of pain including a constant deep, aching, or burning pain; a paroxysmal, lancinating pain; hyperalgesia (painful stimuli are more painful than expected); and allodynia (pain associated with typically non-painful stimuli). The pharmacological treatment of PHN may include a variety of medications including alpha-2 delta ligands (gabapentin and pregabalin), other anticonvulsants (carbamazepine), tricyclic antidepressants (amitriptyline, nortriptyline, doxepin), topical analgesics (5 % lidocaine patch, capsaicin) tramadol, or other opioids. The considerable side effect profiles of the commonly used oral medications often limit their practical use, and a combination of both topical and systemic agents may be required for optimal outcomes. Physicians and other treatment providers must tailor treatment based on the response of individual patients.

Neuropathic pain is pain that arises as a direct consequence of a lesion or diseases affecting the somatosensory system. Treatments for neuropathic pain include pharmacological, nonpharmacological, and interventional therapies. Currently recommended first-line pharmacological treatments include antidepressants and anticonvulsants (gabapentin and pregabalin). However, in some cases, pharmacological therapy alone fails to give adequate control of the chronic pain. New techniques have been invented and have been proved effective on neuropathic pain, such as behavioral, cognitive, integrative, and physical therapies. In this review, we focused on the advances in the treatment of central neuropathic pain, diabetic peripheral neuropathy, postherpetic neuralgia, and cancer pain.

Unlabelled: To understand how patient demographics and patient-reported disease characteristics relate to successful management of postherpetic neuralgia (PHN), integrated data from phase 3 and phase 4 studies of patients with PHN (n = 546) who received once-daily gastroretentive gabapentin (G-GR, 1800 mg) were analyzed. There were widespread, networked, positive correlations among efficacy end points--pain qualities on the visual analog scale (VAS) and Brief Pain Inventory (BPI), measures of pain interference on the BPI, and Patient Global Impression of Change (PGIC)--most likely characterized by positive feedback loops, in which pain interferes with patient functioning, and poor functioning enhances pain. VAS scores at baseline or at week 2 were the strongest predictors of being "much" or "very much" improved on the PGIC; BPI sleep interference scores were the strongest predictors of percent changes in BPI pain qualities and in the average of BPI interference scores, whereas age, sex, and race were not important predictors. In addition to VAS, BPI sleep interference and PGIC assessments appeared to be key co-strategic factors important for successful treatment outcomes, and should be considered as co-primary end points in future clinical trials of PHN. This could improve detection of true positive efficacy responses and guide successful transition to real-world clinical practice., Perspective: This study describes complex relationships among measures of pain intensity, pain interference with daily activities, and demographics of patients with PHN treated with G-GR. Such comprehensive characterization provides important insight into how different variables contribute to successful treatment, and may lead to better management of neuropathic pain., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Herpes zoster is a frequent painful infectious disease whose incidence and severity increase with age. In older people, there is a strong bidirectional link between herpes zoster and functional decline, which refers to a decrement in ability to perform activities of daily living due to ageing and disabilities. However, the exact nature of such link remains poorly established. Based on the opinion from a multidisciplinary group of experts, we here propose a new model to account for the interplay between infection, somatic/psychiatric comorbidity, coping skills, polypharmacy, and age, which may account for the functional decline related to herpes zoster in older patients. This model integrates the risk of decompensation of underlying disease; the risk of pain becoming chronic (e.g. postherpetic neuralgia); the risk of herpes zoster non-pain complications; the detrimental impact of herpes zoster on quality of life, functioning, and mood; the therapeutic difficulties due to multimorbidity, polypharmacy, and ageing; and the role of stressful life events in the infection itself and comorbid depression. This model underlines the importance of early treatment, strengthening coping, and vaccine prevention.

Herpes zoster (HZ), a common vesiculo-erythematous skin disease associated with reactivation of varicella zoster virus in the cranial nerve, dorsal root, and autonomic ganglia, is accompanied by several related symptoms represented by postherpetic neuralgia. Among them, involvement of vesicorectal dysfunction is relatively rare. The vesicorectal symptom can usually be recovered in transient course, but is quite important in terms of impaired quality of life. Male individuals affected with HZ and skin lesions on sacral dermatome have been reported as independent risk factors of zoster-related voiding dysfunction. In this study, urinary symptoms were focused upon and six patients with zoster-related voiding dysfunction at a single faculty of dermatology in Japan from 2009 to 2014 were retrospectively analyzed. All patients showed HZ lesions on the sacral area and the urinary symptom recovered in approximately 2 months (14 days to 7 months). The term of treatment for zoster-associated urinary dysfunction was positively correlated with that for zoster-related pain without significance (r = 0.661, P = 0.153). Average treatment term for pain relief of sacral HZ accompanied by voiding dysfunction (91.3 ± 76.44 days) was significantly longer than that of sacral HZ without urinary symptom (18.9 ± 20.42 days) (P = 0.032). These results suggested that zoster-related voiding dysfunction would mainly be involved in sacral HZ and closely associated with severity of zoster-related pain. Dermatologists should be aware that severe zoster-related pain accompanied by sacral HZ, which is related to prolonged treatment of pain relief, can be a predictive factor of voiding dysfunction., (© 2015 Japanese Dermatological Association.)

Vitamin D is renowned for its pleiotropic effects, including but not limited to bone integrity, and it has assumed an important role in the current research era. As vitamin D receptors are present in a variety of human tissues, particularly immune cells, the immunomodulatory potential of vitamin D cannot be overemphasized. Herpes zoster, which presents as grouped cutaneous vesicles over dermatomes or visceral/central nervous system infection in its severe form, has a higher incidence in immune-suppressed patients. Considering the importance of vitamin D in host immunity, we hypothesize that vitamin D acts as an effect-modifier for the entire herpes zoster spectrum with regard to disease susceptibility, manifestation, efficacy of pharmacologic management, and emergent complications during treatment. Moreover, the possibility exists that vitamin D might affect the course of postherpetic neuralgia. In line with this theory, we comprehensively searched the existing herpes zoster literature and provided important insight into the relationship between the disease courses of herpes zoster and vitamin D., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: A pilot study has shown that real-time fMRI (rtfMRI) neurofeedback could be an alternative approach for chronic pain treatment. Considering the relative small sample of patients recruited and not strictly controlled condition, it is desirable to perform a replication as well as a double-blinded randomized study with a different control condition in chronic pain patients. Here we conducted a rtfMRI neurofeedback study in a subgroup of pain patients - patients with postherpetic neuralgia (PHN) and used a different sham neurofeedback control. We explored the feasibility of self-regulation of the rostral anterior cingulate cortex (rACC) activation in patients with PHN through rtfMRI neurofeedback and regulation of pain perception., Methods: Sixteen patients (46-71 years) with PHN were randomly allocated to a experimental group (n = 8) or a control group (n = 8). 2 patients in the control group were excluded for large head motion. The experimental group was given true feedback information from their rACC whereas the control group was given sham feedback information from their posterior cingulate cortex (PCC). All subjects were instructed to perform an imagery task to increase and decrease activation within the target region using rtfMRI neurofeedback., Results: Online analysis showed 6/8 patients in the experimental group were able to increase and decrease the blood oxygen level dependent (BOLD) fMRI signal magnitude during intermittent feedback training. However, this modulation effect was not observed in the control group. Offline analysis showed that the percentage of BOLD signal change of the target region between the last and first training in the experimental group was significantly different from the control group's and was also significantly different than 0. The changes of pain perception reflected by numerical rating scale (NRS) in the experimental group were significantly different from the control group. However, there existed no significant correlations between BOLD signal change and NRS change., Conclusion: Patients with PHN could learn to voluntarily control over activation in rACC through rtfMRI neurofeedback and alter their pain perception level. The present study may provide new evidence that rtfMRI neurofeedback training may be a supplemental approach for chronic clinical pain management.

A 64-year-old male patient with a history of herpes zoster exposure presented with severe, constant, burning pain in the left T10 dermatome consistent with postherpetic neuralgia. Previous treatment included oral and topical medications as well as an intercostal nerve block; however, these treatment options did not provide significant relief. The patient was treated with a single-level T10 thoracic transforaminal epidural steroid injection for refractory postherpetic neuralgia. He reported complete resolution of his symptoms at 2- and 12-week follow-ups. This case illustrates transforaminal epidural steroid injections may be a successful treatment option for postherpetic neuralgia., (Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Understanding the effect of postherpetic neuralgia (PHN) pain on brain activity is important for clinical strategies. This is the first study, to our knowledge, to relate PHN pain to small-world properties of brain functional networks. Functional magnetic resonance imaging (fMRI) was used to construct functional brain networks of the subjects during the resting state. Sixteen patients with PHN pain and 16 (8 males, 8 females for both groups) age-matched controls were studied. The PHN patients exhibited decreased local efficiency along with non-significant changes of global efficiency in comparison with the healthy controls. Moreover, regional nodal efficiency was found to be significantly affected by PHN pain in the areas related to sense (postcentral gyrus, inferior parietal gyrus and thalamus), memory/affective processes (parahippocampal gyrus) and emotional activities (putamen). Significant correlation (p<0.05) was also found between the nodal efficiency of putamen and pain intensity in PHN patients. Our results suggest that PHN modulates the local efficiency, and the small-world properties of brain networks may have potentials to objectively evaluate pain information in clinic., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Age- and gender-matched reference values are essential for the clinical use of quantitative sensory testing (QST). To extend the standard test sites for QST-according to the German Research Network on Neuropathic Pain-to the trunk, we collected QST profiles on the back in 162 healthy subjects. Sensory profiles for standard test sites were within normal interlaboratory differences. QST revealed lower sensitivity on the upper back than the hand, and higher sensitivity on the lower back than the foot, but no systematic differences between these trunk sites. Age effects were significant for most parameters. Females exhibited lower pressure pain thresholds (PPT) than males, which was the only significant gender difference. Values outside the 95% confidence interval of healthy subjects (considered abnormal) required temperature changes of >3.3-8.2 °C for thermal detection. For cold pain thresholds, confidence intervals extended mostly beyond safety cutoffs, hence only relative reference data (left-right differences, hand-trunk differences) were sufficiently sensitive. For mechanical detection and pain thresholds, left-right differences were 1.5-2.3 times more sensitive than absolute reference data. The most sensitive parameter was PPT, where already side-to-side differences >35% were abnormal. Compared to trunk reference data, patients with postherpetic neuralgia exhibited thermal and tactile deficits and dynamic mechanical allodynia, mostly without reduced mechanical pain thresholds. This pattern deviates from other types of neuropathic pain. QST reference data for the trunk will also be useful for patients with postthoracotomy pain or chronic back pain., (Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Objective: Bee venom has been reported to have antinociceptive and anti-inflammatory effects in experimental studies. However, questions still remain regarding the clinical use of bee venom. This report describes the successful outcome of bee venom treatment for refractory postherpetic neuralgia., Patient: A 72-year-old Korean man had severe pain and hypersensitivity in the region where he had developed a herpes zoster rash 2 years earlier. He was treated with antivirals, painkillers, steroids, and analgesic patches, all to no effect., Intervention: The patient visited the East-West Pain Clinic, Kyung Hee University Medical Center, to receive collaborative treatment. After being evaluated for bee venom compatibility, he was treated with bee venom injections. A 1:30,000 diluted solution of bee venom was injected subcutaneously along the margins of the rash once per week for 4 weeks., Results: Pain levels were evaluated before every treatment, and by his fifth visit, his pain had decreased from 8 to 2 on a 10-point numerical rating scale. He experienced no adverse effects, and this improvement was maintained at the 3-month, 6-month, and 1-year phone follow-up evaluations., Conclusion: Bee venom treatment demonstrates the potential to become an effective treatment for postherpetic neuralgia. Further large-sample clinical trials should be conducted to evaluate the overall safety and efficacy of this treatment.

Neuralgia (neuropathy) is the most common manifestation of herpes zoster (HZ). In spinal and cranial neuralgia, there are 3 types of pain: 1) spontaneous, persistent, burning pain; 2) intermittent sharp pain; 3) pain occurring with nonpainful stimulation. The skin exhibits areas of hypesthesia, anesthesia, and dysesthesia. Ophthalmic neuralgia (of the first branch of the trigeminal nerve) is encountered in 20% of HZ cases. HZ of the auricle and external auditory meatus concurrent with facial and vestibulocochlear neuropathy is diagnosed as Ramsay Hunt syndrome. Postherpetic neuralgia (neuropathy) is characterized by pain present for 3 months or more after the appearance of herpetic eruptions. Combined therapy involving the earlier use of antiviral agents, tricyclic antidepressants, analgesics, and neuromidine is the most effective option for HZ-induced neuralgia (neuropathy).

Objectives: Neuropathic pain is often worse at night; however, little is known about pain rhythmicity during waking hours. We aimed to replicate previous observations of diurnal pain progression, evaluate associations between diurnal rhythmicity and clinical factors, and evaluate the impact of diurnal rhythmicity on treatment response., Methods: We performed exploratory analyses of 2 trials (The New England Journal of Medicine 2005; 352:1324; The Lancet 2009; 374:1252) in diabetic neuropathy and postherpetic neuralgia. Pain recorded at 8:00 AM, 4:00 PM, and 8:00 PM, at baseline and during drug treatment was examined., Results: Data from the latest trial replicated our previous observation of diurnal pain progression with a relative pain intensity difference of 33% between 8:00 AM and 8:00 PM. This pattern was preserved during treatment with gabapentin, nortriptyline, and their combination. Pooled multivariable analyses suggested that difference in pain intensity from 8:00 AM to 8:00 PM was more pronounced in females (vs. males) and in diabetic peripheral neuropathy (vs. postherpetic neuralgia). The baseline magnitude of pain intensity difference from 8:00 AM to 8:00 PM failed to predict treatment response., Discussion: These observations suggest that neuropathic pain progressively increases throughout the day with clinically relevant morning-evening differences and further indicate that sex and underlying etiology may be important determinants of diurnal rhythmicity in neuropathic pain. Consideration of these patterns may guide improved therapeutic strategies and stimulate new directions of research that will improve our understanding and treatment of neuropathic pain.

This article describes the clinical findings of cranial neuralgias, such as trigeminal neuralgia, glossopharyngeal neuralgia, nervus intermedius neuralgia, and others, and postherpetic neuralgia. Pathophysiology of these neuralgias, diagnostic methods, and treatment are also discussed. This information will enable the dentist to diagnose patients who have these rare conditions., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: In patients with chronic pain due to diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN), pregabalin treatment results in pain relief and improved patient function/quality of life (QoL). Few studies, however, have examined the exact relationship between pain relief and improvements in patient function/QoL. It is unclear, for example, whether pregabalin has a direct independent effect on patient function/QoL or whether improvements in function/QoL are an indirect consequent of pain relief., Objectives: To determine whether improvements in function/QoL in response to pregabalin treatment are related to the extent of pain relief in patients with neuropathic pain due to DPN or PHN and to determine whether pregabalin has a direct independent effect on patient function/QoL that is distinct from its effects on pain., Methods: Data from 11 randomized, double-blind, placebo-controlled trials of pregabalin for the treatment of DPN or PHN were pooled for this analysis. Changes in patient function/QoL scores were plotted according to the extent of pain relief to assess whether greater levels of pain relief were associated with greater improvement in function/QoL. A novel mediation analysis was used to asses to what extent the effects of pregabalin on function/QoL scores are a direct treatment effect as opposed to an indirect effect mediated through improvements in pain or sleep., Results: Moderate-to-substantial pain relief (a ≥30% decrease in pain) in response to pregabalin treatment was associated with significant (P < 0.05) improvements in 36-Item Short Form Health Survey (SF-36) scores (used to assess patient function/QoL). In many patients, greatest improvement in SF-36 scores was reported by patients achieving ≥50% decrease in pain. Analysis of Patient Global Impression of Change scores revealed a similar trend, where >80% of patients who achieved substantial pain relief also reported their status as much or very much improved. A substantial direct pregabalin treatment effect was evident for many SF-36 domains that could not be explained by pain relief or improvement in sleep., Conclusions: In patients with chronic pain due to DPN or PHN, improvements in patient function/QoL in response to pregabalin treatment are correlated with the extent of pain relief. However, such improvements in function/QoL are not mediated entirely through pain relief but are the result of a combination of pregabalin's effects on pain and sleep disturbance and a direct effect on patient function itself., (Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.)

Herpes zoster and its sequela post-herpetic neuralgia (PHN) are conditions with significant morbidity. PHN is a chronic, debilitating neuropathic pain that can persist long beyond resolution of visible cutaneous manifestations. This paper provides practical guidelines for management of herpes zoster and PHN. For herpes zoster, antivirals should be started, preferably within 72 h of onset, to reduce the severity and duration of the eruptive phase and to reduce the intensity of acute pain. PHN can be treated with either topical or systemic agents. Topical lidocaine and capsaicin are effective. For patients with more severe pain, the following systemic agents can be considered (in decreasing order of recommendation): the anticonvulsants gabapentin and pregabalin, the tricyclic antidepressants amitriptyline, nortriptyline, and desipramine, and, lastly, the opioid analgesics tramadol, morphine, oxycodone, and methadone. For patients at high risk of developing PHN, early initiation of gabapentin or amitriptyline after the onset of herpes zoster is suggested. The new zoster vaccine has been shown to be effective in reducing the incidence of herpes zoster and PHN.

Background: Postherpetic neuralgia (PHN) is a common complication of herpes zoster and remains a challenging condition of neuropathic pain. Allodynia, a prominent feature of PHN, extends beyond the margins of the initial rash area. In the present study, we investigated the association between cutaneous denervation and the development of postherpetic allodynia and hyperalgesia by using a murine model of PHN., Methods: Female C57BL/6j mice were used. Herpes simplex virus type-1 (HSV1) was inoculated on the unilateral shin, a region that is predominantly innervated by L3 dorsal root ganglion (DRG) neurons. After the zoster-like skin lesions healed, mice were classified by the presence of mechanical allodynia and hyperalgesia in the plantar aspect of the ipsilateral hindpaw. Scarred lumbar (innervated by L2-4 DRG neurons) and the ipsilateral plantar (innervated by L3-5 DRG neurons) skin sections were immunostained with an antibody against protein gene product (PGP)9.5. The number of PGP9.5-immunoreactive (IR) profiles in the epidermis and dermis were analyzed for quantification of cutaneous innervation., Results: In the epidermis of the scarred lumbar skin, the intraindividual mean number of PGP9.5-IR profiles was significantly decreased in mice inoculated with HSV1. The intraindividual maximum and mean numbers of PGP9.5-IR profiles in the epidermis of the scarred skin were not significantly different between mice with and without postherpetic allodynia and hyperalgesia. In the dermis of the scarred lumbar skin, the intraindividual maximum and mean numbers of PGP9.5-IR profiles were significantly decreased in mice with postherpetic allodynia and hyperalgesia, but not in mice without these symptoms. The intraindividual minimum number of PGP9.5-IR profiles in the dermis and epidermis was significantly decreased by HSV1 inoculation. HSV1 inoculation significantly decreased the intraindividual mean number of PGP9.5-IR profiles in the epidermis, but not dermis, of the plantar skin on the inoculated side., Conclusions: The present results suggest that the severity of dermal denervation in the scarred skin is associated with the development of postherpetic allodynia and hyperalgesia that extend beyond the margins of the initial rash area. The decrease of epidermal nerve density in the scarred and stimulation skins may not be associated with postherpetic allodynia and hyperalgesia.

The present work is based on literature data from PubMed. Neuropathic pain is caused by a lesion or disease of the somatosensory system. Peripheral and central sensitization play a crucial role in its pathomechanism. The clinical symptoms are mainly characterized by burning and throbbing pain and sensory disturbances like hyperalgesia and allodynia. Therapeutic recommendations are antidepressants, antiepileptics, opioids and neuro-stimulation methods.

The efficacy of first-line therapeutic agents for postherpetic neuralgia (PHN) has been established in randomized, controlled clinical trials. However, pain in PHN is often refractory to treatment. Many of the patients with PHN are elderly, with additional issues of polypharmacy and comorbidity. They experience various types of pain, suggesting that more than 1 pathophysiologic pain mechanism is involved. PHN adversely affects health-related quality of life. Up to this point, no single best treatment has been identified for PHN. Pharmacological treatments for PHN are inadequate, and many patients are undertreated. Suboptimal treatment can be related to intolerable side effects of medications, long titration periods to reach the effective dosage, inadequate dosing, poor compliance with dosing schedules, and low treatment satisfaction. Inadequate therapeutic response leads more than half the patients with PHN treated with either gabapentin or pregabalin to switch to another class of medication, and more than 30% of patients to add on another class of medication. Safety and tolerability are important considerations in therapy, especially in the elderly. Few patients with PHN and physicians are satisfied with the currently available treatments. Thus, the effective management of postherpetic neuralgia remains an ongoing challenge. New and improved treatment options are therefore needed for the effective management of PHN.

This article investigates the effects of postherpetic neuralgia (PHN) on resting-state brain activity utilizing arterial spin labeling (ASL) techniques. Features of static and dynamic cerebral blood flow (CBF) were analyzed to reflect the specific brain response to PHN pain. Eleven consecutive patients suffering from PHN and 11 age- and gender-matched control subjects underwent perfusion functional magnetic resonance imaging brain scanning during the resting state. Group comparison was conducted to detect the regions with significant changes of CBF in PHN patients. Then we chose those regions that were highly correlated with the self-reported pain intensity as "seeds" to calculate the functional connectivity of both groups. Absolute CBF values of these regions were also compared across PHN patients and control subjects. Significant increases in CBF of the patient group were observed in left striatum, right thalamus, left primary somatosensory cortex (S1), left insula, left amygdala, left primary somatomotor cortex, and left inferior parietal lobule. Significant decreases in CBF were mainly located in the frontal cortex. Regional CBF in the left caudate, left insula, left S1, and right thalamus was highly correlated with the pain intensity, and further comparison showed that the regional CBF in these regions is significantly higher in PHN groups. Functional connectivity results demonstrated that the reward circuitry involved in striatum, prefrontal cortex, amygdala, and parahippocampal gyrus and the circuitry among striatum, thalamus, and insula were highly correlated with each element in PHN patients. In addition, noninvasive brain perfusion imaging at rest may provide novel insights into the central mechanisms underlying PHN pain., (Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Questions from patients about analgesic pharmacotherapy and responses from the authors are presented to help educate patients and make them more effective self-advocates. The topics addressed in this issue are postherpetic neuralgia and capsaicin and a discussion about symptoms, causes, and treatments is presented.