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.

(-)-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.

[Efficacy observation of treating diabetic nephropathy by shenshuaining granule combined telmisartan tablet].

OBJECTIVE: To observe the effect of Shenshuaining Granule (SG) combined telmisartan on serum creatinine (SCr) levels and urinary albumin contents in diabetic nephropathy (DN) patients, and to explore its efficacy. METHODS: Totally 204 DN patients were recruited, and further assigned to 3 groups, i.e., the early DN group, the clinical stage of DN with normal renal function group, the clinical stage of DN with insufficient renal function group. Patients in the same group were randomly allocated to the telmisartan treatment group, the SG treatment group, and the combination of SG and telmisartan treatment group, 68 in each group. Patients in the telmisartan treatment group took telmisartan tablet, 80 mg per day, once daily. Those in the SG treatment group took SG, 5 g each time, 3 times per day. Those in the combination of SG and telmisartan treatment group took telmisartan tablet (80 mg per day, once daily) and SG (5 g each time, 3 times per day). The therapeutic course for all was 3 successive months. SCr levels, serum urea nitrogen (BUN),24 h urine microalbumin (24 h U-MA) were detected before and after treatment. Results In three different treatment groups, 24 h U-MA decreased after treatment in the telmisartan treatment group; SCr and BUN decreased after treatment in the SG treatment group; and 24 h U-MA, SCr and BUN decreased after treatment in the combination of SG and telmisartan treatment group (P<0.05). In the clinical stage of DN with insufficient renal function group, SCr obviously increased after treatment in the telmisartan treatment group (P <0. 05). In the 3 DN stages, SCr and 24 h U-MA obviously decreased in the combination of SG and telmisartan treatment group, when compared with the telmisartan treatment group and the SG treatment group (P<0.05). Compared with the telmisartan treatment group, SCr and BUN obviously decreased in the SG treatment group, but 24 h U-MA quantitation obviously increased (P<0.05). BUN obviously decreased in the combination of SG and telmisartan treatment group (P<0. 05). CONCLUSION: The combination of SG and telmisartan could decrease urinary albumin, and stabilize SCr levels.

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.

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.

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.

Short-term spinal cord stimulation is an effective therapeutic approach for herpetic-related neuralgia-A Chinese nationwide expert consensus.

Purpose: Short-term spinal cord stimulation (st-SCS) has been widely used to treat herpetic-related neuralgia (HN) in China for several years, but is still heavily debated as it has no strong evidence in clinical application. Therefore, a questionnaire survey among the Chinese pain specialist workgroup of the Chinese Neuromodulation Society and Chinese Medical Doctor Association was carried out to achieve a consensus about the clinical use of st-SCS for HN treatment. Methods: The contents of the questionnaire include basic information about doctors (hospital level, work experience, training, procedure numbers, etc.), efficacy, indications, and contraindications of st-SCS, operation conditions, and preoperative preparation of st-SCS, and the prospect of the st-SCS procedure. Initially, the survey was conducted on 110 experts who have practiced the st-SCS procedure from all over the provinces in China. Finally, valuable data was calculated from the 110 questionnaires excluding the doctors with <1 year of experience of st-SCS, <10 cases of procedures per year, and no standard training in SCS technique. Results: Based on the 110 questionnaires, it is estimated that 5,000 to 10,000 cases of electrical stimulation are carried out nationwide each year. Sixty-nine valid questionnaires acquired from senior pain physicians were more valuable and specialized in the efficacy, indications, and contraindications of st-SCS for HN. It was commonly agreed (97.10%) that the HN patients with <3 months will obtain good effectiveness (patient satisfaction rate ≥50%). Almost all (98.55%) agreed that st-SCS can be used in SHN patients, there was a common agreement (72.46%) that AHN patients are an indication of st-SCS, and more than half agreement (53.62%) that st-SCS may be fit for early PHN (3-6 months). A common agreement (79.71%) was achieved that more than half of HN patients had the experience of nerve block or nerve pulsed RF. A similarly large number of experts 57/69 (82.61%) agreed that an 80% paresthesia coverage should be achieved at the test stimulation and 57/69 (82.61%) agreed that the treatment of st-SCS need be persistent for 1-2 weeks. Conclusions: Early HN patients can get an effective outcome from the treatment of st-SCS and maybe the indication of st-SCS. Moreover, standardized training for pain physicians and basic research and clinical studies are warranted.

Direct Inhibition of Microglia Activation by Pretreatment With Botulinum Neurotoxin A for the Prevention of Neuropathic Pain.

Peripheral injection of botulinum neurotoxin A (BoNT/A) has been demonstrated to have a long-term analgesic effect in treating neuropathic pain. Around peripheral nerves, BoNT/A is taken up by primary afferent neurons and inhibits neuropeptide release. Moreover, BoNT/A could also be retrogradely transported to the spinal cord. Recent studies have suggested that BoNT/A could attenuates neuropathic pain by inhibiting the activation of spinal glial cells. However, it remains unclear whether BoNT/A directly interacts with these glial cells or via their interaction with neurons. Our aim here is to determine the direct effect of BoNT/A on primary microglia and astrocytes. We show that BoNT/A pretreatment significantly inhibits lipopolysaccharide (LPS) -induced activation and pro-inflammatory cytokine release in primary microglia (1 U/mL BoNT/A in medium), while it has no effect on the activation of astrocytes (2 U/mL BoNT/A in medium). Moreover, a single intrathecal pre-administration of a low dose of BoNT/A (1 U/kg) significantly prohibited the partial sciatic nerve ligation (PSNL)- induced upregulation of pro-inflammatory cytokines in both the spinal cord dorsal horn and dorsal root ganglions (DRGs), which in turn prevented the PSNL-induced mechanical allodynia and thermal hyperalgesia. In conclusion, our results indicate that BoNT/A pretreatment prevents PSNL-induced neuropathic pain by direct inhibition of spinal microglia activation.

Transcriptome Analysis Reveals the Role of Cellular Calcium Disorder in Varicella Zoster Virus-Induced Post-Herpetic Neuralgia.

As a typical neuropathic pain, post-herpetic neuralgia (PHN) is a common complication of herpes zoster (HZ), which seriously affects the normal life and work of patients. The unclear pathogenesis and lack of effective drugs make the clinical efficacy of PHN unsatisfactory. Here, we obtained the transcriptome profile of neuroblastoma cells (SH-SY5Y) and DRG in rats infected with varicella zoster virus (VZV) by transcriptome sequencing (RNA-Seq) combined with publicly available gene array data sets. Next, the data processing of the transcriptome map was analyzed using bioinformatics methods, including the screening of differentially expressed genes (DEGs), Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, real-time fluorescent quantitative PCR (qRT-PCR) was used to detect the expression of calcium-related genes, and calcium fluorescent probes and calcium colorimetry were used to evaluate the distribution and content of calcium ions in cells after VZV infection. Transcriptome data analysis (GO and KEGG enrichment analysis) showed that calcium disorder played an important role in SH-SY5Y cells infected by VZV and dorsal root ganglion (DRG) of the PHN rat model. The results of qRT-PCR showed that the expression levels of calcium-related genes BHLHA15, CACNA1F, CACNG1, CHRNA9, and STC2 were significantly upregulated, while the expression levels of CHRNA10, HRC, and TNNT3 were significantly downregulated in SH-SY5Y cells infected with VZV. Our calcium fluorescent probe and calcium colorimetric test results showed that VZV could change the distribution of calcium ions in infected cells and significantly increase the intracellular calcium content. In conclusion, our results revealed that the persistence of calcium disorder caused by VZV in nerve cells might be a crucial cause of herpetic neuralgia, and a potential target for clinical diagnosis and treatment of PHN.

Change in Cav3.2 T-Type Calcium Channel Induced by Varicella-Zoster Virus Participates in the Maintenance of Herpetic Neuralgia.

Pain, as the most prevalent neurological complication of herpes zoster (HZ), may occur before or during the rash onset or even after the rash has recovered. Particularly, postherpetic neuralgia (PHN) is a refractory chronic condition, usually defined as pain persisting for 3 months or longer from the onset of HZ. Pain evoked by HZ impairs the normal physical and emotional functions of the patients, severely reducing their quality of life. However, how zoster-associated pain occurs and develops into PHN are elusive, making PHN difficult to predict. Uncovering the pathogenesis of zoster-associated pain (or HN) helps us to better understand the onset of PHN and supports developing more effective treatments. In this study, we successfully constructed a model for zoster-associated pain through varicella-zoster virus (VZV) infections of mouse footpads and pain behavior assessments. Next, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Gene Ontology (GO) to analyze PHN rodent dorsal root ganglion (DRG) gene microarray data and found that calcium signal disorder might be involved in the onset of PHN. By using reverse transcription real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting, we confirmed that VZV infection could significantly upregulate the expression of T-type calcium channel Cav3.2 in DRG and spinal dorsal horn (SDH). Intrathecal administration of Cav3.2 blocker (2R/S)-6-prenylnaringenin (6-PNG) relieved mechanical and thermal hyperalgesia induced by VZV. Taken together, our data indicated that VZV might participate in the occurrence and development of HN by upregulating the expression of Cav3.2 in DRG and SDH. These findings will help to reveal the underlying mechanisms on long-lasting pain and PHN formation, providing a new insight that Cav3.2 can be the promising drug target for remitting PHN.

Battlefield Acupuncture for Adult Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Pain is a major public health problem, causing heavy social and economic burdens to patients and society while consuming tremendous medical resources at the same time. Thus, there is a critical need to find low-cost, efficacious, and therapeutic approaches to help manage pain. While acupuncture is increasingly recognized as a promising pain-relieving method, less is known about a specific form of auricular acupuncture known as Battlefield Acupuncture (BFA). The BFA technique involves the sequential placement of semi-permanent, single-use, French ASP[Formula: see text] golden needles to five specific acupoints in one or both ears, where they are left in place for 3-4 days or longer [Niemtzow, R.C., Battlefield acupuncture. Med. Acupunct. 19: 225-228, 2007]. The BFA needles (more accurately described as tiny conical darts) pierce the ear in designated locations in a particular order [Levy, C.E., N. Casler and D.B. FitzGerald. Battlefield acupuncture: an emerging method for easing pain. Am. J. Phys. Med. Rehabil. 97: e18-e19, 2018.]. (Figs. 4 and 5) It was developed by Dr. Richard C. Niemtzow in 2001, as a subgroup form of an auricular acupuncture technique based on the somatotopic arrangement of an inverted fetus pattern on the external ear [Romoli, M. Ear acupuncture: historical abstract-differences of ear cartography between the east and the west. Dtsch. Z. Akupunkt. 53: 24-33, 2010.]. Currently, BFA is widely used in the US military, but to our knowledge, there is no review which comprehensively synthesizes the current publications surrounding pain management. This review aims to investigate the effects and safety of BFA in adults with pain. Electronic databases were searched for randomized controlled trials (RCTs) published in English evaluating efficacy and safety of BFA in adults with pain, from database inception to September 6, 2019. The primary outcome was pain intensity change, and the secondary outcome was safety. Nine RCTs were included in this review, and five trials involving 344 participants were analyzed quantitatively. Compared with no intervention, usual care, sham BFA, and delayed BFA interventions, BFA had no significant improvement in the pain intensity felt by adults suffering from pain. Few adverse effects (AEs) were reported with BFA therapy, but they were mild and transitory. BFA is a safe, rapid, and easily learned acupuncture technique, mainly used in acute pain management, but no significant efficacy was found in adult individuals with pain, compared with the control groups. Given the poor methodological quality of the included studies, high-quality RCTs with rigorous evaluation methods are needed in the future.

Clinical Characteristics, Treatment Effectiveness, and Predictors of Response to Pharmacotherapeutic Interventions Among Patients with Herpetic-Related Neuralgia: A Retrospective Analysis.

BACKGROUND: The treatment for herpetic-related neuralgia focuses on symptom control by use of antiviral drugs, anticonvulsants, and tricyclic antidepressants. We aimed to explore the clinical characteristics associated with medication responsiveness, and to build a classifier for identification of patients who have risk of inadequate pain management. METHODS: We recruited herpetic-related neuralgia patients during a 3-year period. Patients were stratified into a medication-resistant pain (MRP) group when the pain decrease in the visual analogue scale (VAS) is < 3 points, and otherwise a medication-sensitive pain (MSP) group. Multivariate logistic regression was performed to determine the factors associated with MRP. We fitted four machine learning (ML) models, namely logistic regression, random forest, supporting vector machines (SVM), and naïve Bayes with clinical characteristics gathered at admission to identify patients with MRP. RESULTS: A total of 213 patients were recruited, and 132 (61.97%) patients were diagnosed with MRP. Subacute herpes zoster (HZ) (vs. acute, OR 8.95, 95% CI 3.15-29.48, p = 0.0001), severe lesion (vs. mild lesion, OR 3.84, 95% CI 1.44-10.81, p = 0.0084), depressed mood (unit increase OR 1.10, 95% CI 1.00-1.20, p = 0.0447), and hypertension (hypertension, vs. no hypertension, OR 0.36, 95% CI 0.14-0.87, p = 0.0266) were significantly associated with MRP. Among four ML models, SVM had the highest accuracy (0.917) and receiver operating characteristic-area under the curve (0.918) to discriminate MRP from MSP. Phase of disease is the most important feature when fitting ML models. CONCLUSIONS: Clinical characteristics collected before treatment could be adopted to identify patients with MRP.

Percutaneous posterior-lateral lumbar interbody fusion for degenerative disc disease using a B-Twin expandable spinal spacer.

Degenerative disc disease (DDD) causes gradual intervertebral space collapse, concurrent discogenic or facet-induced pain, and possible compression radiculopathy. A new minimal invasion procedure of percutaneous posterior-lateral lumbar interbody fusion (PPLIF) using a B-Twin stand-alone expandable spinal spacer (ESS) was designed to treat this disease and evaluated by follow-up more than 1 year. 12 cases with chronic low back pain and compressive radiculopathy due to DDD refractory were selected to conservative treatment. Under fluoroscopy in the posterior-lateral position, a K-wire was advanced into the intervertebral space and a dilator and working cannula were introduced into the disc space step by step. Discectomy and endplate scratching were performed through the cannula using pituitary forceps and endplate curettage. An ESS was inserted into the intervertebral space by a B-Twin expandable spinal delivery system after some bone graft chips implanted into the disc space. The ongoing study includes intraoperative difficulties, complications, radiologic evidence of fusion and clinical outcome as scored by pre- and postoperative questionnaires pertaining to pain intensity and degree of disability. The 12 procedures of lumbar interbody fusion using stand-alone expandable spinal system through percutaneous approach were successful. Radiologic study demonstrated fusion in a total of 11 cases and only 1 exception after more than 1 year visiting. The values of Visual Analog Scale (VAS) on movement and Oswestry Disability Index (ODI) dropped by more than 80 and 67.4%, respectively. Disk space heights averaging 9.0 mm before procedure were increased to 11.5 mm 1 month (a significant difference compared with preprocedure, P < 0.01) after surgery and stabilized at 10.8 mm upon final follow-up (a significant difference compared with preprocedure, P < 0.01). The results demonstrated that the percutaneous approach for posterior-lateral lumbar interbody fusion using expandable spinal system is a valuable micro-invasion method for the DDD patients and can achieve the same outcome as with other methods.

The Impact of Natural Product Dietary Supplements on Patients with Gout: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Natural product dietary supplements (NPDS) are frequently used for the treatment of gout, but reliable efficacy and safety data are generally lacking or not well organized to guide clinical decision making. This review aims to explore the impacts of NPDS for patients with gout. An electronic literature search was conducted to retrieve data published in English language from databases from inception to August 14, 2019. Randomized controlled trials (RCTs) that compared NPDS with or without placebo, diet modification, conventional pharmaceutics, or the other Chinese medicine treatment for gout patients were included. Two authors screened the articles, extracted the data, and assessed the risk of bias of each included trial independently. Meta-analysis was performed using Review Manager version 5.3.5. Results. Nine RCTS were enrolled in this review. The methodological quality of the nine RCTs was poor. The study results showed that in the majority of trials, NPDS demonstrated some degree of therapeutic efficacy for joint swelling, pain, and activity limitation. In contradistinction, serum uric acid (SUA) level (SMD -1.80, 95% CI: -4.45 to 0.86) (p > 0.05) and CRP levels (N = 232; SMD, -0.26; 95% CI, -0.55 to 0.04) (p > 0.05) did not improve significantly. The incidence of adverse events (AEs) was not lower in the participants treated with NPDS (N = 750; RR, 0.47; 95% CI, 0.20-1.11) (p > 0.05). Conclusion. Current existing evidence is not sufficient to provide clinical guidance regarding the efficacy and safety of NPDS as a treatment for gout due to poor trial quality and lack of standardized evaluation criteria. Larger and more rigorously designed RCTs are needed in the future.