A novel method to simultaneously record spinal cord electrophysiology and electroencephalography signals.

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.

Neurological Causes of Chest Pain.

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.

Deficits in ascending and descending pain modulation pathways in patients with postherpetic neuralgia.

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.

Electrophysiological characteristics of the frontal nerve in patients with herpetic ophthalmic neuralgia.

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.

A Rare Presentation of Cranial Polyneuropathy Without Rash Caused by Varicella Zoster Virus.

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.

Post-herpetic Neuralgia: a Review.

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.

Advances in the Treatment of Neuropathic Pain.

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.

Functional decline and herpes zoster in older people: an interplay of multiple factors.

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-induced neuralgia (neuropathy)].

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).

Association of denervation severity in the dermis with the development of mechanical allodynia and hyperalgesia in a murine model of postherpetic neuralgia.

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.

[New data for the pathomechanism of neuropathic pain: therapeutic evidences]. / Új adatok a neuropátiás fájdalom patomechanizmusához: terápiás evidenciák.

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.

Varicella zoster virus-induced pain and post-herpetic neuralgia in the human host and in rodent animal models.

Pain and post-herpetic neuralgia (PHN) are common and highly distressing complications of herpes zoster that remain a significant public health concern and in need of improved therapies. Zoster results from reactivation of the herpesvirus varicella zoster virus (VZV) from a neuronal latent state established at the primary infection (varicella). PHN occurs in some one fifth to one third of zoster cases with severity, incidence, and duration of pain increasing with rising patient age. While VZV reactivation and the ensuing ganglionic damage trigger the pain response, the mechanisms underlying protracted PHN are not understood, and the lack of an animal model of herpes zoster (reactivation) makes this issue more challenging. A recent preclinical rodent model has developed that opens up the potential to allow the exploration of the underlying mechanisms and treatments for VZV-induced pain. Rats inoculated with live cell-associated human VZV into the hind paw reliably demonstrate thermal hyperalgesia and mechanical allodynia for extended periods and then spontaneously recover. Dorsal root ganglia express a limited VZV gene subset, including the IE62 regulatory protein, and upregulate expression of markers suggesting a neuropathic pain state. The model has been used to investigate treatment modalities and aspects of pain signaling and is under investigation by the authors to delineate VZV genetics involved in the induction of pain. This article compares human zoster-associated pain and PHN to the pain indicators in the rat and poses important questions that, if answered, could be the basis for new treatments.

Gustatory dysfunction after mandibular zoster.

Varicella zoster, limited to the mandibular nerve, is rare. Classical symptoms are pain, hypesthesia and vesicular eruption restricted to the third trigeminal segment (V3). Little is known on taste affection after mandibular nerve zoster. We report two cases of patients suffering from mandibular zoster associated with subjective taste disorder. In both cases, gustatory measures confirmed ipsilateral hemiageusia of the anterior two-thirds of the tongue. After 2 months, the symptoms regressed and psychophysical measures came back to normal values, whereas post-zoster neuralgia lasted for more than 1 year. Gustatory dysfunction is a possible symptom after mandibular nerve zoster. In contrast to post-zoster neuralgia, taste function seems to recover quickly.

Efficacy of thermotherapy for herpes zoster and postherpetic neuralgia: A protocol for systemic review and meta-analysis.

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.

Structural and functional brain abnormalities in postherpetic neuralgia: A systematic review of neuroimaging studies.

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.

The brain's structural differences between postherpetic neuralgia and lower back pain.

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

Somesthetic, gustatory, olfactory function and salivary flow in patients with neuropathic trigeminal pain.

OBJECTIVES: To determine somesthetic, olfactory, gustative and salivary abnormalities in patients with burning mouth syndrome (BMS), idiopathic trigeminal neuralgia (ITN) and trigeminal postherpetic neuralgia (PHN). SUBJECTS AND METHODS: Twenty patients from each group (BMS, ITN, PHN) and 60 healthy controls were evaluated with a systematized quantitative approach of thermal (cold and warm), mechanical, pain, gustation, olfaction and salivary flow; data were analyzed with ANOVA, Tukey, Kruskal-Wallis and Dunn tests with a level of significance of 5%. RESULTS: There were no salivary differences among the groups with matched ages; the cold perception was abnormal only at the mandibular branch of PHN (P = 0.001) and warm was abnormal in all trigeminal branches of PHN and BMS; mechanical sensitivity was altered at the mandibular branch of PHN and in all trigeminal branches of BMS. The salty, sweet and olfactory thresholds were higher in all studied groups; the sour threshold was lower and there were no differences of bitter. CONCLUSION: All groups showed abnormal thresholds of gustation and olfaction; somesthetic findings were discrete in ITN and more common in PHN and BMS; central mechanisms of balance of sensorial inputs might be underlying these observations.

Does skin temperature difference as measured by infrared thermography within 6 months of acute herpes zoster infection correlate with pain level?

BACKGROUND: Changes in the temperature distribution of the skin follows herpes zoster (HZ). Infrared thermography is a non-invasive, non-ionizing diagnostic tool that provides information about normal and abnormal functioning of the sensory and sympathetic nervous systems. This study examined the usefulness of infrared thermography as a predictor of post-herpetic neuralgia (PHN). METHODS: Infrared thermography was performed on the affected body regions of 110 patients who had been diagnosed with acute HZ. Demographic data collected included age, gender, time of skin lesions onset, development of PHN, and comorbidities. The temperature differences between the unaffected and affected dermatome were calculated. Differences >0.6 degrees C for the mean temperature across the face and trunk were considered abnormal. RESULTS: The affected side was warmer in 35 patients and cooler in 33 patients than the contralateral side. A patient's age and disease duration affected treatment outcomes. However, the temperature differences were not correlated with pain severity, disease duration, allodynia, development of PHN, and use of antiviral agents (P>0.05). CONCLUSION: A patient's age and disease duration are the most important factors predicting PHN progression, irrespective of thermal findings, and PHN cannot be predicted by infrared thermal imaging.

The placebo response: relationship to outcomes in trials of postherpetic neuralgia.

Placebo responses in controlled studies of neuropathic pain, including postherpetic neuralgia, have increased in recent years and may obscure benefits of potential treatments. Investigations of the basis of the placebo effect have revealed some of the anatomical and physiological substrates for these responses. Placebo responses are accompanied by changes in activity in brain regions involved in analgesia, pain processing, reward and emotion, and they involve neurotransmitters with well established roles in pain modulation, including opioids and cholecystokinin. These findings may eventually provide useful suggestions for limiting placebo responses in clinical trials as identification of the cues that contribute to placebo responses could conceivably permit their avoidance in the design of clinical studies. Analyses of the characteristics of clinical trials in neuropathic pain have revealed some factors that might also help explain the increase in placebo responses. These factors include the longer duration of contemporary trials and recruitment practices of high-enrolling study centres. In trials of patients with postherpetic neuralgia, inclusion of patients with a short duration of post-zoster pain can result in a high rate of spontaneous remission that can contribute to an apparent 'placebo response'. Future placebo-controlled trials of treatments for postherpetic neuralgia may need to consider modifications of the design and conduct of these studies to maximize the chance of obtaining valid study results.