Transcriptome analysis reveals dysregulation of inflammatory and neuronal function in dorsal root ganglion of paclitaxel-induced peripheral neuropathy rats.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most common side-effect of anti-cancer therapy. To date, there are no clinically effective analgesics that could prevent and treat CIPN. However, the exact pathogenesis of CIPN is still unclear. In the present study, we use the paclitaxel-induced peripheral neuropathy (PIPN) model, aiming to better understand the transcriptomic level of the Dorsal root ganglia (DRG) neurons in rats with PIPN. mRNA from each DRG sample was reverse transcribed to cDNA and sequenced using next-generation high throughput sequencing technology. Quantitative RT-PCR verification was used to confirm the identified Differentially expressed genes (DEGs) in the DRG of PIPN rats. RNAseq results have identified 384 DEGs (adjusted P-value < 0.05; fold change ≥ 2) in the DRG of rats 14 days after paclitaxel injection in total, including 97 up-regulated genes, and 287 down-regulated genes. GO analysis revealed that these DEGs were majorly involved in neuropeptide activity, chemokine receptor activity, defense response, and inflammatory response. Kyoto Encyclopedia of Gene and Genomes analysis showed that neuroactive ligand-receptor interaction and cytokine-cytokine receptor interaction were involved in sensory neurons of rats with PIPN. Besides, comparison analysis identified that 11 DEGs in the PIPN model are shared with either inflammatory pain (Ces1d, Cfd, Retn, and Fam150b) or neuropathic pain (Atf3, Csrp3, Ecel1, Gal, Sprr1a, Tgm1, and Vip). Quantitative RT-PCR results also confirmed the validation of the RNAseq data. These results suggested that neuroactive ligand-receptor interaction and cytokine-cytokine receptor interaction are majorly involved in sensory neurons of rats with PIPN. Immune, inflammatory responses and neuron functional changes are the major pathogenesis of PIPN. Paclitaxel-induced peripheral neuropathy has shared characteristics with both inflammatory pain and neuropathic pain.

HSV-1 infection-induced herpetic neuralgia involves a CCL5/CCR5-mediated inflammation mechanism.

Herpetic-related neuralgia (HN) caused by varicella-zoster virus (VZV) infection is one of the most typical and common neuropathic pain in the clinic. However, the potential mechanisms and therapeutic approaches for the prevention and treatment of HN are still unclear. This study aims to provide a comprehensive understanding of the molecular mechanisms and potential therapeutic targets of HN. We used an HSV-1 infection-induced HN mouse model and screened the differentially expressed genes (DEGs) in the DRG and spinal cord using an RNAseq technique. Moreover, bioinformatics methods were used to figure out the signaling pathways and expression regulation patterns of the DEGs enriched. In addition, quantitative real-time RT-PCR and western blot were carried out to further confirm the expression of DEGs. HSV-1 inoculation in mice resulted in mechanical allodynia, thermal hyperalgesia, and cold allodynia, following the infection of HSV-1 in both DRG and spinal cord. Besides, HSV-1 inoculation induced an up-regulation of ATF3, CGRP, and GAL in DRG and activation of astrocytes and microglia in the spinal cord. Moreover, 639 genes were upregulated, 249 genes were downregulated in DRG, whereas 534 genes were upregulated and 12 genes were downregulated in the spinal cord of mice 7 days after HSV-1 inoculation. GO and KEGG enrichment analysis suggested that immune responses and cytokine-cytokine receptor interaction are involved in DRG and spinal cord neurons in mice after HSV-1 infection. In addition, CCL5 and its receptor CCR5 were significantly upregulated in DRG and spinal cord upon HSV-1 infection in mice. And blockade of CCR5 exhibited a significant analgesic effect and suppressed the upregulation of inflammatory cytokines in DRG and spinal cord induced by HSV-1 infection in mice. HSV-1 infection-induced allodynia and hyperalgesia in mice through dysregulation of immune response and cytokine-cytokine receptor interaction mechanism. Blockade of CCR5 alleviated allodynia and hyperalgesia probably through the suppression of inflammatory cytokines. Therefore, CCR5 could be a therapeutic target for the alleviation of HSV-1 infection-induced HN.

SARS-CoV-2, SARS-CoV, and MERS-CoV encode circular RNAs of spliceosome-independent origin.

Circular RNAs (circRNAs) are a newly recognized component of the transcriptome with critical roles in autoimmune diseases and viral pathogenesis. To address the importance of circRNA in RNA viral transcriptome, we systematically identified and characterized circRNAs encoded by the RNA genomes of betacoronaviruses using both bioinformatical and experimental approaches. We predicted 351, 224, and 2764 circRNAs derived from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV, and Middle East respiratory syndrome coronavirus, respectively. We experimentally identified 75 potential SARS-CoV-2 circRNAs from RNA samples extracted from SARS-CoV-2-infected Vero E6 cells. A systematic comparison of viral and host circRNA features, including abundance, strand preference, length distribution, circular exon numbers, and breakpoint sequences, demonstrated that coronavirus-derived circRNAs had a spliceosome-independent origin. We further showed that back-splice junctions (BSJs) captured by inverse reverse-transcription polymerase chain reaction have different level of resistance to RNase R. Through northern blotting with a BSJ-spanning probe targeting N gene, we identified three RNase R-resistant bands that represent SARS-CoV-2 circRNAs that are detected cytoplasmic by single-molecule and amplified fluorescence in situ hybridization assays. Lastly, analyses of 169 sequenced BSJs showed that both back-splice and forward-splice junctions were flanked by homologous and reverse complementary sequences, including but not limited to the canonical transcriptional regulatory sequences. Our findings highlight circRNAs as an important component of the coronavirus transcriptome, offer important evaluation of bioinformatic tools in the analysis of circRNAs from an RNA genome, and shed light on the mechanism of discontinuous RNA synthesis.

(-)-menthol increases excitatory transmission by activating both TRPM8 and TRPA1 channels in mouse spinal lamina II layer.

(-)-menthol, a major form of menthol, is one of the most commonly used chemicals. Many studies have demonstrated that (-)-menthol produces analgesic action through peripheral mechanisms which are mainly mediated by activation of TRPM8. Moreover, intrathecal injection of menthol induces analgesia as well. However, the central actions and mechanisms of (-)-menthol remain unclear. Here, we have investigated the action of (-)-menthol on excitatory synaptic transmission in spinal lamina II layer which plays a pivotal role in modulating nociceptive transmission from the periphery by using patch-clamp technique in mice spinal cord. We found that (-)-menthol increased miniature excitatory postsynaptic current frequency. The frequency increases which (-)-menthol induced were in a dose-dependent manner (EC50: 0.1079 mM). However, neither genetic knockout nor pharmacological inhibition of TRPM8 could block (-)-menthol-induced effects entirely. Furthermore, this increase was also impaired by TRPA1 antagonist HC030031, but abolished utterly by co-application of TRPM8 and TRPA1 antagonist. Our results indicate that (-)-menthol increases the excitatory synaptic transmission by activating either TRPA1 or TRPM8 channels in spinal lamina II layer.

Gene expression changes of thermo-sensitive transient receptor potential channels in obese mice.

Adipose tissues play key roles in energy homeostasis. Brown adipocytes and beige adipocytes in white adipose tissue (WAT) share the similar characters of thermogenesis, both of them could be potential targets for obesity management. Several thermo-sensitive transient receptor potential channels (thermoTRPs) are shown to be involved in adipocyte biology. However, the expression pattern of thermoTRPs in adipose tissues from obese mice is still unknown. The mRNA expression of thermoTRPs in subcutaneous WAT (sWAT) and interscapular brown adipose tissue (iBAT) from lean and obese mice were measured using reverse transcriptase-quantitative PCRs (RT-qPCR). The results demonstrated that all 10 thermoTRPs are expressed in both iBAT and sWAT, and without significant difference in the mRNA expression level of thermoTRPs between these two tissues. Moreover, Trpv1 and Trpv3 mRNA expression levels in both iBAT and sWAT were significantly decreased in high fat diet (HFD)-induced obese mice and db/db (leptin receptor deficient) mice. Trpm2 mRNA expression level was significantly decreased only in sWAT from HFD-induced obese mice and db/db mice. On the other hand, Trpv2 and Trpv4 mRNA expression levels in iBAT and sWAT were significantly increased in HFD-induced obese mice and db/db mice. Taken together, we conclude that all 10 thermoTRPs are expressed in iBAT and sWAT. And several thermoTRPs differentially expressed in adipose tissues from HFD-induced obese mice and db/db mice, suggesting a potential involvement in anti-obesity regulations.

A Randomized Comparative Study of Pulsed Radiofrequency Treatment With or Without Selective Nerve Root Block for Chronic Cervical Radicular Pain.

BACKGROUND: We demonstrated a combination of pulsed radiofrequency (PRF) and cervical nerve root block (CNRB) via a posterior approach was superior to a transforaminal epidural steroid injection through the anterolateral approach for cervical radicular pain in a previous study. This randomized trial was conducted to determine the comparative efficacy between CNRB, PRF, and CNRB + PRF for cervical radicular pain. METHODS: A prospective and randomized design was used in this study. Sixty-two patients were randomized into three parallel groups: CNRB, PRF, or CNRB + PRF. Numeric Rating Scale (NRS) was used to measure pain intensity, and global perceived effect (GPE) was scored by the patient on a 7-point scale, ranging from much worse (-3), no change (0), to total improvement (+3). The outcomes were evaluated at 1 week, 1 month, 3 months, and 6 months. Side effects and complications were noted. RESULTS: The NRS was significantly reduced in all three groups 1 week after the treatments (P < 0.001), and the rates of positive GPE (+2 or +3) were not significantly different between the three groups. At 1, 3, and 6 months of follow-ups, the combined therapy achieved significantly lower NRS and higher GPE compared to CNRB or PRF alone group (P < 0.001). There were no significant differences between the CNRB and PRF groups (P > 0.05). No serious complications were observed in any of the patients. CONCLUSIONS: Combining CNRB and PRF appeared to be a safe and efficacious technique for cervical radicular pain. The combination therapy yielded better outcomes than either CNRB or PRF alone.

Hospitalized pain patients have recently doubled: a retrospective case series study in Shenzhen Nanshan People's Hospital of China.

AIM: To study the characteristics of hospitalized pain patients in Shenzhen with the aim of identifying some of the social, economic and therapeutic aspects of pain management in China. METHODS: A retrospective study was designed to collect the information of 3061 hospitalized pain patients in 2003, 2007 and 2011. Their demographic characteristics, diagnoses of pain types, hospitalization, therapeutic effect, economic cost and payment types were analyzed. RESULTS: The number of female patients significantly increased with time. The patient's average age increased from 41.3 in 2003 to 49.7 years old in 2011. The most common diagnosis of pain was lumbar intervertebral disc herniation. The total hospitalization days of each patient per year significantly decreased from 15.7 days in 2003 to 10.4 days in 2011. However, the hospitalization cost for each patient was almost doubled. CONCLUSION: The hospitalized pain patients and their economic burdens have almost been doubled in the recent four years.

Combining Botulinum Toxin (A) Injection With Peripheral Nerve Stimulation in a Patient for Intractable Ophthalmic Postherpetic Neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is a particularly challenging neuropathic pain condition, especially when it involves the trigeminal nerve. Peripheral nerve stimulation (PNS) can provide 50-70% improvement in pain to many who fail medical management. However, this pain relief can be incomplete, and residual pain may persist for many years. Here we report a case that was successfully managed by a novel technique of combining supraorbital nerve stimulation with botulinum toxin type A (BTA) for intractable ophthalmic PHN. CASE: A 73-year-old man presented with burning, stabbing, constant, severe pain in the ophthalmic branch of left trigeminal nerve dermatome, which had been present for a year. A permanent PNS provided 50% pain relief, but there was residual pain in the left orbital area that has remained, which was refractory to pharmaceutical treatment. Because of the restricted location of the residual pain, this patient was an appropriate candidate for BTA injection. RESULTS: Following the BTA injection, the patient had a significant improvement in pain relief and this continued for six months without any oral medication. CONCLUSIONS: In a patient with trigeminal PHN, local injection of BTA effectively reduced pain remaining after treatment with PNS.

Lanatoside C inhibits herpes simplex virus 1 replication by regulating NRF2 distribution within cells.

BACKGROUND: In the past decades, extensive research has been conducted to identify new drug targets for the treatment of Herpes simplex virus type 1 (HSV-1) infections. However, the emergence of drug-resistant HSV-1 strains remains a major challenge. This necessitates the identification of new drugs with novel mechanisms of action. Lanatoside C (LanC), a cardiac glycoside (CG) approved by the US Food and Drug Administration (FDA), has demonstrated anticancer and antiviral properties. Nevertheless, its potential as an agent against HSV-1 infections and the underlying mechanism of action are currently unknown. PURPOSE: This study aimed to investigate the antiviral activity of LanC against HSV-1 and elucidate its molecular mechanisms. METHODS: The in vitro antiviral activity of LanC was assessed by examining the levels of viral genes, proteins, and virus titers in HSV-1-infected ARPE-19 and Vero cells. Immunofluorescence (IF) analysis was performed to determine the intracellular distribution of NRF2. Additionally, an in vivo mouse model of HSV-1 infection was developed to evaluate the antiviral activity of LanC, using indicators such as intraepidermal nerve fibers (IENFs) loss and viral gene inhibition. RESULTS: Our findings demonstrate that LanC significantly inhibits HSV-1 replication both in vitro and in vivo. The antiviral effect of LanC is mediated by the perinuclear translocation of NRF2. CONCLUSIONS: LanC exhibits anti-HSV-1 effects in viral infections, which are associated with the intracellular translocation of NRF2. These findings suggest that LanC has the potential to serve as a novel NRF2 modulator in the treatment of viral diseases.

Identification and characterization of Varicella Zoster Virus circular RNA in lytic infection.

This study investigates the role of circular RNAs (circRNAs) in the context of Varicella-Zoster Virus (VZV) lytic infection. We employ two sequencing technologies, short-read sequencing and long-read sequencing, following RNase R treatment on VZV-infected neuroblastoma cells to identify and characterize both cellular and viral circRNAs. Our large scanning analysis identifies and subsequent experiments confirm 200 VZV circRNAs. Moreover, we discover numerous VZV latency-associated transcripts (VLTs)-like circRNAs (circVLTslytic), which contain multiple exons and different isoforms within the same back-splicing breakpoint. To understand the functional significance of these circVLTslytic, we utilize the Bacteria Artificial Chromosome system to disrupt the expression of viral circRNAs in genomic DNA location. We reveal that the sequence flanking circVLTs' 5' splice donor plays a pivotal role as a cis-acting element in the formation of circVLTslytic. The circVLTslytic is dispensable for VZV replication, but the mutation downstream of circVLTslytic exon 5 leads to increased acyclovir sensitivity in VZV infection models. This suggests that circVLTslytic may have a role in modulating the sensitivity to antiviral treatment. The findings shed new insight into the regulation of cellular and viral transcription during VZV lytic infection, emphasizing the intricate interplay between circRNAs and viral processes.

Botulinum toxin type A reduces hyperalgesia and TRPV1 expression in rats with neuropathic pain.

OBJECTIVE: We aim to determine the effects of botulinum toxin type A (BTX-A) on the thresholds of pain and the expression of transient receptor potential vanilloid type 1 (TRPV1) in the dorsal root ganglion (DRG) in rats with neuropathic pain induced by selective ventral root transection (VRT). METHODS: Neuropathic pain was induced by transection of the lumbar 5 ventral root in male Sprague-Dawley rats. BTX-A or saline was administered to the plantar surface by subcutaneous injection. SB366791 (an inhibitor of TRPV1) was administered intraperitoneally. Behavioral tests were conducted preoperatively and at predefined postoperative days. The expression of TRPV1 was detected and quantified by immunohistochemistry and Western blotting at postoperative days 3, 7, 14, and 21. RESULTS: TRPV1 expression increased significantly in the L4 ∼5 dorsal root ganglia 7 days after L5 VRT compared with the sham-operated control (P < 0.05). This increase persisted for at least 21 days. The thresholds of foot withdrawal to mechanical and thermal stimulation decreased significantly as well. Subcutaneous injection of BTX-A significantly and dose-dependently reduced the expression of TRPV1 (P < 0.05) and partially reversed the pain thresholds. CONCLUSION: Upregulation of TRPV1 expression in the DRG is an important mechanism of neuropathic pain induced by the VRT. The analgesic effect of BTX-A is most likely mediated through reduction of TRPV1 expression in the nociceptors.

Rodent models of postherpetic neuralgia: How far have we reached?

Background: Induced by varicella zoster virus (VZV), postherpetic neuralgia (PHN) is one of the common complications of herpes zoster (HZ) with refractory pain. Animal models play pivotal roles in disclosing the pain mechanisms and developing effective treatments. However, only a few rodent models focus on the VZV-associated pain and PHN. Objective: To summarize the establishment and characteristics of popular PHN rodent models, thus offer bases for the selection and improvement of PHN models. Design: In this review, we retrospect two promising PHN rodent models, VZV-induced PHN model and HSV1-induced PHN model in terms of pain-related evaluations, their contributions to PHN pathogenesis and pharmacology. Results: Significant difference of two PHN models is the probability of virus proliferation; 2) Most commonly used pain evaluation of PHN model is mechanical allodynia, but pain-induced anxiety and other behaviours are worth noting; 3) From current PHN models, pain mechanisms involve changes in virus gene and host gene expression, neuroimmune-glia interactions and ion channels; 4) antiviral drugs and classical analgesics serve more on the acute stage of herpetic pain. Conclusions: Different PHN models assessed by various pain evaluations combine to fulfil more comprehensive understanding of PHN.

Comparative Transcriptome of Dorsal Root Ganglia Reveals Distinct Etiologies of Paclitaxel- and Oxaliplatin-induced Peripheral Neuropathy in Rats.

Chemotherapy-induced peripheral neuropathy is one of the most common side effects of anticancer therapy. It is anticipated that chemotherapies with different mechanisms of action may affect somatosensory neurons differently. This study aimed to explore similar and differential etiologies of oxaliplatin- and paclitaxel-induced neuropathy by comparing the transcriptomes of dorsal root ganglia (DRGs). We retrieved our previously published transcriptome data of DRGs extracted from vehicle-, oxaliplatin- and paclitaxel-treated rats (GSE160543), to analyze in parallel the differentially expressed genes (DEGs) and Gene ontology (GO) terms enrichment. We found that both oxaliplatin and paclitaxel treatments consistently produced mechanical allodynia, thermal hyperalgesia, and cold hyperalgesia in rats. Compared to vehicle, 320 and 150 DEGs were identified after oxaliplatin and paclitaxel treatment, respectively. Only 17 DEGs were commonly dysregulated by the two reagents. Activating transcription factor 3 (Atf3), a marker of nerve injury, was elevated only after paclitaxel treatment. GO analysis suggested that paclitaxel treatment was associated with neuronal changes characterized by numerous terms that are related to synaptic transmission, while oxaliplatin was more likely to affect dividing cells (e.g., the glia) and neuroinflammation. Notably, 29 biological processes GO terms were commonly enriched in response to both drugs. However, 28 out of 29 terms were oppositely modulated. This study suggests that distinct mechanisms underly paclitaxel- and oxaliplatin-induced neuropathy. Paclitaxel might directly affect somatosensory neurons while oxaliplatin primarily targets dividing cells and immune cells.

Up-regulation of oxytocin receptors on peripheral sensory neurons mediates analgesia in chemotherapy-induced neuropathic pain.

BACKGROUND AND PURPOSE: Chemotherapy-induced neuropathic pain (CINP) currently has limited effective treatment. Although the roles of oxytocin (OXT) and the oxytocin receptor (OXTR) in central analgesia have been well documented, the expression and function of OXTR in the peripheral nervous system remain unclear. Here, we evaluated the peripheral antinociceptive profiles of OXTR in CINP. EXPERIMENTAL APPROACH: Paclitaxel (PTX) was used to establish CINP. Quantitative real-time polymerase chain reaction (qRT-PCR), in situ hybridization, and immunohistochemistry were used to observe OXTR expression in dorsal root ganglia (DRG). The antinociceptive effects of OXT were assessed by hot-plate and von Frey tests. Whole-cell patch clamp was performed to record sodium currents, excitability of DRG neurons, and excitatory synapse transmission. KEY RESULTS: Expression of OXTR in DRG neurons was enhanced significantly after PTX treatment. Activation of OXTR exhibited antinociceptive effects, by decreasing the hyperexcitability of DRG neurons in PTX-treated mice. Additionally, OXTR activation up-regulated the phosphorylation of protein kinase C (pPKC) and, in turn, impaired voltage-gated sodium currents, particularly the voltage-gated sodium channel 1.7 (NaV 1.7) current, that plays an indispensable role in PTX-induced neuropathic pain. OXT suppressed excitatory transmission in the spinal dorsal horn as well as excitatory inputs from primary afferents in PTX-treated mice. CONCLUSION AND IMPLICATIONS: The OXTR in small-sized DRG neurons is up-regulated in CINP and its activation relieved CINP by inhibiting the neural excitability by impairment of NaV 1.7 currents via pPKC. Our results suggest that OXTR on peripheral sensory neurons is a potential therapeutic target to relieve CINP.

Combining Regional and Connectivity Metrics of Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging for Individualized Prediction of Pain Sensitivity.

Characterization and prediction of individual difference of pain sensitivity are of great importance in clinical practice. MRI techniques, such as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), have been popularly used to predict an individual's pain sensitivity, but existing studies are limited by using one single imaging modality (fMRI or DTI) and/or using one type of metrics (regional or connectivity features). As a result, pain-relevant information in MRI has not been fully revealed and the associations among different imaging modalities and different features have not been fully explored for elucidating pain sensitivity. In this study, we investigated the predictive capability of multi-features (regional and connectivity metrics) of multimodal MRI (fMRI and DTI) in the prediction of pain sensitivity using data from 210 healthy subjects. We found that fusing fMRI-DTI and regional-connectivity features are capable of more accurately predicting an individual's pain sensitivity than only using one type of feature or using one imaging modality. These results revealed rich information regarding individual pain sensitivity from the brain's both structural and functional perspectives as well as from both regional and connectivity metrics. Hence, this study provided a more comprehensive characterization of the neural correlates of individual pain sensitivity, which holds a great potential for clinical pain management.

Treatment Efficacy and Technical Advantages of Temporary Spinal Nerve Root Stimulation Compared to Traditional Spinal Cord Stimulation for Postherpetic Neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is a common complication after herpes zoster infection. While conventional dorsal column temporary spinal cord stimulation (tSCS) has been shown as an effective treatment option for this pain condition, recent data suggests ipsilateral temporary spinal nerve root stimulation (tSNRS) as a safe alternative for treating PHN. However, there is no direct clinical comparison between the newer tSNRS and the traditional tSCS. OBJECTIVES: The current retrospective study aimed to describe the technical factors and the therapeutic efficacy of tSNR for patients with unilateral PHN and to compare these parameters with those treated with tSCS. STUDY DESIGN: Retrospective cohort study. SETTING: Single-center study in a large academic hospital. METHODS: One hundred sixty patients with unilateral PHN who underwent 7-14 days of tSCS (n = 109) or tSNRS (n = 51) treatment were included. Technical factors between the 2 groups, such as procedure time, radiation dosage, number of electrodes used, number of stimulation parameter adjustments, and average cost, were compared. Treatment efficacy, measured by analgesic coverage, pain visual analog scale (VAS), total analgesic agent consumption, Pittsburgh sleep quality index (PSQI), and physical and mental quality of life, were also compared between the 2 groups at baseline, post-procedure, and 3 months after stimulation treatment. RESULTS: Patients who underwent tSNRS reported significant improvement in pain level, sleep quality, and overall quality of life immediately postprocedure and during the follow-up period. This therapeutic effect was comparable to the tSCS group. Moreover, tSNRS achieved this therapeutic effect with a fewer number of implanted electrodes and stimulation adjustments than tSCS. The precision and consistency of the tSNRS technique were associated with a significant overall lower cost, a shorter procedure time, and less intraoperative radiation exposure in the tSNRS group than in those who received tSCS. LIMITATIONS: The current retrospective cohort study was limited by its relatively short follow-up period. Also, the selection of stimulation techniques was not randomized. CONCLUSIONS: While tSNRS provides similar therapeutic efficacy compared to tSCS for patients with unilateral PHN; it offers several technical advantages. These advantages include shorter procedure time, less radiation exposure, fewer implanted electrodes, more effective stimulation, and lower overall cost.

EEG Beta-Band Spectral Entropy Can Predict the Effect of Drug Treatment on Pain in Patients With Herpes Zoster.

BACKGROUND: Medication is the main approach for early treatment of herpes zoster, but it could be ineffective in some patients. It is highly desired to predict the medication responses to control the degree of pain for herpes zoster patients. The present study is aimed to elucidate the relationship between medication outcome and neural activity using EEG and to establish a machine learning model for early prediction of the medication responses from EEG. METHODS: The authors acquired and analyzed eye-closed resting-state EEG data 1 to 2 days after medication from 70 herpes zoster patients with different drug treatment outcomes (measured 5-6 days after medication): 45 medication-sensitive pain patients and 25 medication-resistant pain patients. EEG power spectral entropy of each frequency band was compared at each channel between medication-sensitive pain and medication-resistant pain patients, and those features showing significant difference between two groups were used to predict medication outcome with different machine learning methods. RESULTS: Medication-sensitive pain patients showed significantly weaker beta-band power spectral entropy in the central-parietal regions than medication-resistant pain patients. Based on these EEG power spectral entropy features and a k-nearest neighbors classifier, the medication outcome can be predicted with 80% ± 11.7% accuracy, 82.5% ± 14.7% sensitivity, 77.7% ± 27.3% specificity, and an area under the receiver operating characteristic curve of 0.85. CONCLUSIONS: EEG beta-band power spectral entropy in the central-parietal region is predictive of the effectiveness of drug treatment on herpes zoster patients, and it could potentially be used for early pain management and therapeutic prognosis.

Three-Day Continuous Oxytocin Infusion Attenuates Thermal and Mechanical Nociception by Rescuing Neuronal Chloride Homeostasis via Upregulation KCC2 Expression and Function.

Oxytocin (OT) and its receptor are promising targets for the treatment and prevention of the neuropathic pain. In the present study, we compared the effects of a single and continuous intrathecal infusion of OT on nerve injury-induced neuropathic pain behaviours in mice and further explore the mechanisms underlying their analgesic properties. We found that three days of continuous intrathecal OT infusion alleviated subsequent pain behaviours for 14 days, whereas a single OT injection induced a transient analgesia for 30 min, suggesting that only continuous intrathecal OT attenuated the establishment and development of neuropathic pain behaviours. Supporting this behavioural finding, continuous intrathecal infusion, but not short-term incubation of OT, reversed the nerve injury-induced depolarizing shift in Cl- reversal potential via restoring the function and expression of spinal K+-Cl- cotransporter 2 (KCC2), which may be caused by OT-induced enhancement of GABA inhibitory transmission. This result suggests that only continuous use of OT may reverse the pathological changes caused by nerve injury, thereby mechanistically blocking the establishment and development of pain. These findings provide novel evidence relevant for advancing understanding of the effects of continuous OT administration on the pathophysiology of pain.

Chinese expert consensus on minimally invasive interventional treatment of trigeminal neuralgia.

Background and purpose: Trigeminal neuralgia is a common condition that is associated with severe pain, which seriously affects the quality of life of patients. When the efficacy of drugs is not satisfactory or adverse drug reactions cannot be tolerated, minimally invasive interventional therapy has become an important treatment because of its simple operation, low risk, high repeatability and low cost. In recent years, minimally invasive interventional treatments, such as radiofrequency thermocoagulation (RF) of the trigeminal nerve and percutaneous microcompression (PMC), have been widely used in the clinic to relieve severe pain in many patients, however, some related problems remain to be addressed. The Pain Association of the Chinese Medical Association organizes and compiles the consensus of Chinese experts to standardize the development of minimally invasive interventional treatment of trigeminal neuralgia to provide a basis for its clinical promotion and application. Materials and methods: The Pain Association of the Chinese Medical Association organizes the Chinese experts to compile a consensus. With reference to the evidence-based medicine (OCEBM) system and the actual situation of the profession, the Consensus Development Committee adopts the nominal group method to adjust the recommended level. Results: Precise imaging positioning and guidance are the keys to ensuring the efficacy and safety of the procedures. RF and PMC are the most widely performed and effective treatments among minimally invasive interventional treatments for trigeminal neuralgia. Conclusions: The pain degree of trigeminal neuralgia is severe, and a variety of minimally invasive intervention methods can effectively improve symptoms. Radiofrequency and percutaneous microcompression may be the first choice for minimally invasive interventional therapy.