Curcumin analogue NL04 inhibits spinal cord central sensitization in rats with bone cancer pain by inhibiting NLRP3 inflammasome activation and reducing IL-1ß production.

The management and therapy of bone cancer pain (BCP) remain formidable clinical challenges. Curcumin and its analogues have been shown to have anti-inflammatory and analgesic properties. In the present study, we investigated the efficacy of curcumin analogue NL04 (NL04) in modulating inflammation in spinal dorsal horn (SDH), thereby exploring its potential to reduce central sensitization of BCP in a rat model. Differing doses of NL04 and curcumin were administered intrathecally either once (on day 12 of BCP) or over seven consecutive days (from day 6-12 of BCP). Results indicated that the ED50 for NL04 and curcumin ameliorating BCP-induced mechanical hyperalgesia is 49.08 µg/kg and 489.6 µg/kg, respectively. The analgesic effects at various doses of NL04 lasted between 4 and 8 h, with sustained administration over a week maintaining pain relief for 1-4 days, while also ameliorating locomotor gait via gait analysis and reducing depressive and anxiety-like behaviors via open-field and light-dark transition tests. The analgesic effects at various doses of curcumin lasted 4 h, with sustained administration over a week maintaining pain relief for 0-2 days. ELISA, Western blotting, qPCR, and immunofluorescence assays substantiated that intrathecal administration of NL04 on days 6-12 of BCP dose-dependently lowered spinal IL-1ß and IL-18 levels and significantly reduced the expression of IKKß genes and proteins, as well as the downstream cleavage of the trans-Golgi network (TGN). Whole-cell patch-clamp results demonstrated that NL04 inhibits potassium ion efflux in rat primary spinal neurons. Thus, NL04 exhibits significant analgesic effects in a BCP rat model by downregulating IKKß expression and inhibiting neuronal potassium ion efflux, which, in turn, suppresses the activation of NLRP3 inflammasomes and reduces IL-1ß production, potentially ameliorating pain management in BCP.

Extent and Resistance Patterns of Gram-negative Bacteria Isolated From 13 Hospitals in Shaoxing, Zhejiang Province.

Gram-negative bacteria are increasingly recognized as the sauce of severe infections. In recent years, epidemiological data has indicated that the drug resistance rate of Gram-negative bacteria has significantly increased. We analyzed the epidemiological surveillance data of gram-negative bacteria in Shaoxing City in 2021 by retrospectively collecting drug susceptibility data of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Burkholderia cepacian from thirteen tertiary hospitals. A total of 24,142 strains were collected from thirteen hospitals. The isolation rates of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, P. mirabilis, E. cloacae, and B. cepacian were 29.25%, 18.83%, 11.03%, 8.43%, 3.80%, 3.12%, and 0.75%, respectively. Among them, 2.86% were carbapenem-resistant E. coli, 12.98% were CRKP, 31.27% were CRPA, and 34.77% were CRAB. Carbapenem-resistant Enterobacterales were more sensitive to ceftazidime-avibactam and polymyxin. The drug resistance rates of P. aeruginosa and A. baumannii to polymyxin were 0 and 1.3%, but the resistance rates to ceftazidime-avibactam were 10.5% and 26.0%, respectively. Based on results from epidemiological data, CRKP had a high isolation rate and non-fermenting bacteria had a high resistance rate to ceftazidime-avibactam. All hospitals should strengthen monitoring and enact continuous intervention to reduce the generation and spread of drug-resistant bacteria.

LncRNA 51325 Alleviates Bone Cancer Induced Hyperalgesia Through Inhibition of Pum2.

Background: Bone cancer pain (BCP) represents one of the most challenging comorbidities associated with cancer metastasis. Long non-coding RNAs (lncRNAs) have garnered attention as potential therapeutic agents in managing neuropathic pain. However, their role in the regulation of nociceptive information processing remains poorly understood. In this study, we observed a significant down-regulation of the spinal lncRNA ENSRNOG00000051325 (lncRNA51325) in a rat model of bone cancer pain. Our study sought to elucidate the potential involvement of lncRNA51325 in the development of BCP by modulating the expression of molecules associated with pain modulation. Methods: We established the BCP model by injecting Walker 256 cells into the tibial plateau of rats. We conducted tests on the pain behaviors and anxiety-like responses of rats through von-Frey test, Gait analysis, and Open Field Test. Spinal lumbar expansion was harvested for molecular biology experiments to explore the relationship between lncRNA51325 and Pumilio RNA binding family member 2 (Pum2). Results: Notably, the overexpression of lncRNA51325 effectively attenuated mechanical allodynia in rats afflicted with BCP, whereas the knockdown of lncRNA51325 induced pain behaviors and anxiety-like responses in naïve rats. Additionally, we observed a time-dependent increase in the expression of Pum2 in BCP-afflicted rats, and intrathecal injection of Pum2-siRNA alleviated hyperalgesia. Furthermore, our investigations revealed that lncRNA51325 exerts a negative modulatory effect on Pum2 expression. The overexpression of lncRNA51325 significantly suppressed Pum2 expression in BCP rats, while the knockdown of lncRNA51325 led to elevated Pum2 protein levels in the spinal cord of naïve rats. Subsequent treatment with Pum2-siRNA mitigated the downregulation of lncRNA51325-induced mechanical allodynia in naïve rats. Conclusion: Our findings indicate that lncRNA51325 plays a role in regulating bone cancer pain by inhibiting Pum2 expression, offering a promising avenue for novel treatments targeting nociceptive hypersensitivity induced by bone metastatic cancer.

Soluble urokinase plasminogen activator receptor is associated with cardiovascular calcification in peritoneal dialysis patients.

BACKGROUND: Cardiovascular disease (CVD) is an important cause of morbidity and mortality in peritoneal dialysis (PD) patients. Cardiovascular calcification (CVC) is highly prevalent in PD patients and could predict their cardiovascular mortality. Soluble urokinase plasminogen activator receptor (suPAR) is closely associated with coronary artery calcification in hemodialysis patients and is an important predictor of CVD. However, the role of suPAR in PD patients is poorly understood. We investigated the relationship between serum suPAR and CVC in PD patients. METHODS: Abdominal aortic calcification (AAC) was assessed by lateral lumbar radiography, coronary artery calcification (CAC) by multi-slice computed tomography, and cardiac valvular calcification (ValvC) by echocardiography. CVC was defined as confirmed presence of calcification in one site (AAC, CAC, or ValvC). Patients were divided into CVC group and non-CVC group. Demographic characteristics, biochemical variables, comorbidities, PD regimen, serum suPAR, and medication were compared between the two groups. Logistic regression was conducted to determine association between serum suPAR and presence of CVC. The receiver-operator curve (ROC) was plotted to calculate the area under the curve (AUC) for suPAR to identify CVC and ValvC. RESULTS: Of 226 PD patients, 111 (49.1%) had AAC, 155 (68.6%) had CAC, and 26 (11.5%) had ValvC. There were significant differences in age, BMI, diabetes, white blood cell, phosphorus, hs-CRP, suPAR, time on dialysis, total volume of dialysate, ultrafiltration, volume of urine, and Kt/V between CVC and non-CVC group. Serum suPAR was associated with CVC by multivariate logistic regression analysis in PD patients, especially in elderly patients. The levels of serum suPAR were closely related to the degree of AAC, CAC, and ValvC in PD patients. The incidence of CVC was higher in patients with higher levels of suPAR. The ROC curve showed that serum suPAR had a predictive value for CVC (AUC = 0.651), especially for ValvC (AUC = 0.828). CONCLUSION: Cardiovascular calcification is prevalent in PD patients. High levels of serum suPAR are associated with cardiovascular calcification in PD patients, especially in elderly patients.

JAG-1/Notch signaling axis in the spinal cord contributes to bone cancer pain in rats.

Notch signal plays an important role in regulating cell-cell interactions with the adjacent cells. However, it remains unknown whether Jagged1 (JAG-1) mediated Notch signaling regulates bone cancer pain (BCP) via the spinal cell interactions mechanism. Here, we showed that intramedullary injection of Walker 256 breast cancer cells increased the expression of JAG-1 in spinal astrocytes and knockdown of JAG-1 reduced BCP. The supplementation of exogenous JAG-1 to the spinal cord induced BCP-like behavior and promoted expression of c-Fos and hairy and enhancer of split homolog-1 (Hes-1) in the spinal cord of the naïve rats. These effects were reversed when the rats were administered intrathecal injections of N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT). The intrathecal injection of DAPT reduced BCP and inhibited Hes-1 and c-Fos expression in the spinal cord. Furthermore, our results showed that JAG-1 up-regulated Hes-1 expression by inducing the recruitment of Notch intracellular domain (NICD) to the RBP-J/CSL-binding site located within the Hes-1 promoter sequence. Finally, the intrathecal injection of c-Fos-antisense oligonucleotides (c-Fos-ASO) and administration of sh-Hes-1 to the spinal dorsal horn also alleviated BCP. The study indicates that inhibition of the JAG-1/Notch signaling axis may be a potential strategy for the treatment of BCP.

ZBP1 and heatstroke.

Heatstroke, which is associated with circulatory failure and multiple organ dysfunction, is a heat stress-induced life-threatening condition characterized by a raised core body temperature and central nervous system dysfunction. As global warming continues to worsen, heatstroke is expected to become the leading cause of death globally. Despite the severity of this condition, the detailed mechanisms that underlie the pathogenesis of heatstroke still remain largely unknown. Z-DNA-binding protein 1 (ZBP1), also referred to as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1, was initially identified as a tumor-associated and interferon (IFN)-inducible protein, but has recently been reported to be a Z-nucleic acid sensor that regulates cell death and inflammation; however, its biological function is not yet fully understood. In the present study, a brief review of the main regulators is presented, in which the Z-nucleic acid sensor ZBP1 was identified to be a significant factor in regulating the pathological characteristics of heatstroke through ZBP1-dependent signaling. Thus, the lethal mechanism of heatstroke is revealed, in addition to a second function of ZBP1 other than as a nucleic acid sensor.

Upregulation of LncRNA71132 in the spinal cord regulates hypersensitivity in a rat model of bone cancer pain.

ABSTRACT: Bone cancer pain (BCP) is a pervasive clinical symptom which impairs the quality life. Long noncoding RNAs (lncRNAs) are enriched in the central nervous system and play indispensable roles in numerous biological processes, while its regulatory function in nociceptive information processing remains elusive. Here, we reported that functional modulatory role of ENSRNOT00000071132 (lncRNA71132) in the BCP process and sponging with miR-143 and its downstream GPR85-dependent signaling cascade. Spinal lncRNA71132 was remarkably increased in the rat model of bone cancer pain. The knockdown of spinal lncRNA71132 reverted BCP behaviors and spinal c-Fos neuronal sensitization. Overexpression of spinal lncRNA71132 in naive rat generated pain behaviors, which were accompanied by increased spinal c-Fos neuronal sensitization. Furthermore, it was found that lncRNA71132 participates in the modulation of BCP by inversely regulating the processing of miR-143-5p. In addition, an increase in expression of spinal lncRNA71132 resulted in the decrease in expression of miR-143 under the BCP state. Finally, it was found that miR-143-5p regulates pain behaviors by targeting GPR85. Overexpression of miR-143-5p in the spinal cord reverted the nociceptive behaviors triggered by BCP, accompanied by a decrease in expression of spinal GPR85 protein, but no influence on expression of gpr85 mRNA. The findings of this study indicate that lncRNA71132 works as a miRNA sponge in miR-143-5p-mediated posttranscriptional modulation of GPR85 expression in BCP. Therefore, epigenetic interventions against lncRNA71132 may potentially work as novel treatment avenues in treating nociceptive hypersensitivity triggered by bone cancer.

Catalpol ameliorates CFA-induced inflammatory pain by targeting spinal cord and peripheral inflammation.

Chronic, inflammatory pain is an international health concern that severely diminishes individuals' quality of life. Catalpol is an iridoid glycoside derived from the roots of Rehmannia glutinosa that possesses anti-inflammatory, antioxidant, and neuroprotective properties for the treating multiple kinds of disorders. Nevertheless, catalpol's impacts on inflammatory pain and its potential methods of action are still unclear. The purpose of this investigation is to determine the mechanism of catalpol to reduce the inflammatory pain behaviors in a rat model with complete Freund's adjuvant (CFA). Catwalk, Von-Frey, and open field testing were performed for behavioral assessment. Western blot analysis and real-time quantitative PCR (RT-PCR) were employed to identify variations in molecular expression, while immunofluorescence was utilized to identify cellular localization. Catalpol effectively reduced CFA-induced mechanical allodynia and thermal hyperalgesia when injected intrathecally. Moreover, catalpol can regulate the HDAC4/PPAR-γ-signaling pathway in CFA rat spinal cord neurons. Meanwhile catalpol significantly decreased the expression of the NF-κB/NLRP3 inflammatory axis in the spinal cord of CFA rats. In addition, both in vivo and in vitro research revealed that catalpol treatment inhibited astrocyte activation and increase inflammatory factor expression. Interestingly, we also found that catalpol could alleviate peripheral pain by inhibiting tissue inflammation. Taken together, the findings declared that catalpol may inhibit inflammatory pain in CFA rats by targeting spinal cord and peripheral inflammation.

CXCR1 participates in bone cancer pain induced by Walker 256 breast cancer cells in female rats.

Bone cancer pain (BCP) is a clinically intractable mixed pain, involving inflammation and neuropathic pain, and its mechanisms remain unclear. CXC chemokine receptor 1 (CXCR1, IL-8RA) and 2 (CXCR2, IL-8RB) are high-affinity receptors for interleukin 8 (IL8). According to previous studies, CXCR2 plays a crucial role in BCP between astrocytes and neurons, while the role of CXCR1 remains unclear. The objective of this study was to investigate the role of CXCR1 in BCP. We found that CXCR1 expression increased in the spinal dorsal horn. Intrathecal injection of CXCR1 siRNA effectively attenuated mechanical allodynia and pain-related behaviors in rats. It was found that CXCR1 was predominantly co-localized with neurons. Intrathecal injection of CXCR1-siRNA reduced phosphorylated JAK2/STAT3 protein levels and the NLRP3 inflammasome (NLRP3, caspase1, and IL-1ß) levels. Furthermore, in vitro cytological experiments confirmed this conclusion. The study results suggest that the spinal chemokine receptor CXCR1 activation mediates BCP through JAK2/STAT3 signaling pathway and NLRP3 inflammasome (NLRP3, caspase1, and IL-1ß).

miR-155-5p in the spinal cord regulates hypersensitivity in a rat model of bone cancer pain.

BACKGROUND: Noncoding microRNAs have emerged as critical players of gene expression in the nervous system, where they contribute to regulating nervous disease. As stated in previous research, the miR-155-5p upregulation happens in the spinal cord at the nociceptive state. It was unclear if miR-155-5p is linked to bone cancer pain (BCP). Herein, we aimed at investigating the miR-155-5p functional regulatory function in BCP process and delineating the underlying mechanism. METHODS: The miRNA-155-5p levels and cellular distribution were determined by RNA sequencing, fluorescent in situ hybridization (FISH), and quantitative real-time PCR (qPCR). Immunoblotting, qPCR, dual-luciferase reporter gene assays, immunofluorescence, recombinant overexpression adeno-associated virus, small interfering RNA, intraspinal administration, and behavioral tests were utilized for exploring the downstream signaling pathway. RESULTS: The miR-155-5p high expression in spinal neurons contributes to BCP maintenance. The miR-155-5p blockage via the intrathecal injection of miR-155-5p antagomir alleviated the pain behavior; in contrast, upregulating miR-155-5p by agomir induced pain hypersensitivity. The miR-155-5p bounds directly to TCF4 mRNA's 3' UTR. BCP significantly reduced protein expression of TCF4 versus the Sham group. The miR-155-5p inhibition relieved the spinal TCF4 protein's down-expression level, while miR-155-5p upregulation by miR-155-5p agomir intrathecal injection decreased TCF4 protein expression in naïve rats. Additionally, TCF4 overexpression in BCP rats could increase Kv1.1. Moreover, TCF4 knockdown inhibited Kv1.1 expression in BCP rats. Indeed, TCF4 and Kv1.1 were co-expressed in BCP spinal cord neurons. CONCLUSION: The study findings stated the miR-155-5p pivotal role in regulating BCP by directly targeting TCF4 in spinal neurons and suggested that miR-155-5p could be a promising target in treating BCP.

Efficacy of Percutaneous Radiofrequency Sympathectomy Versus Percutaneous Ethanol Sympatholysis in the Treatment of Primary Hyperhidrosis.

BACKGROUND: At present, there are many surgical treatments for primary hyperhidrosis (PH), but their medium- and long-term effects remain unclear. OBJECTIVES: To evaluate and compare the efficacy of radiofrequency sympathectomy (RFS) and percutaneous ethanol sympatholysis (PES) in the treatment of PH. STUDY DESIGN: A retrospective study. SETTING: This study was performed at the Affiliated Hospital of Jiaxing University, China. METHODS: Patients who underwent RFS and PES at The First Affiliated Hospital of Jiaxing University for PH were retrospectively reviewed from January 2016 through December 2018 and were divided into an RFS group and a PES group. The Hyperhidrosis Disease Severity Scale  was evaluated at the following time points: before the operation, immediately after the operation, 12 months and 24 months after the operation. The effective rate, patient satisfaction, and compensatory hyperhidrosis were also evaluated. RESULTS: A total of 94 patients diagnosed with primary hyperhidrosis were included (RFS group, n = 45; PES group, n = 49). RFS yielded a postprocedure 24-month effective rate of 53.33% in treating hyperhidrosis compared to PES (24.49%, P < 0.05). There were no significant differences between the 2 groups regarding patient satisfaction (P = 0.927) and compensatory hyperhidrosis (P = 0.711). LIMITATIONS: This was a single-center study. CONCLUSION: This is the first clinical study to evaluate the efficacy of RFS and compare it with PES in treating primary hyperhidrosis. RFS significantly decreased hyperhidrosis and had a higher 2-year effective rate compared to PES.

Correlation Between Electromyography and Severity and Prognosis of Upper Limb Herpes Zoster.

BACKGROUND: There are differences in the clinical treatment schemes for patients with different severities of herpes zoster (HZ). Therefore, effective and accurate evaluation of disease severity is of great significance for the formulation of treatment plans. Postherpetic neuralgia (PHN) with long-term chronic pain leads to anxiety, depression, and even suicidal thoughts, which place a heavy burden on society and the family. Therefore, identifying risk factors and taking early intervention to reduce the occurrence of PHN is meaningful. Electromyography (EMG) can provide technical support for the early diagnosis of peripheral neuropathy. However, the application of EMG in HZ and PHN has rarely been reported. The purpose of this study was to compare the detection indices of EMG in patients with different severities and prognoses of HZ and to analyze the application of EMG in severity and prognosis of HZ. OBJECTIVE: This study aimed to explore the relationship between EMG and severity and prognosis of upper limb HZ. STUDY DESIGN: A retrospective, observational study. SETTING: The study was carried out in the Pain Department of the affiliated Hospital of Jiaxing College in Jiaxing, China. METHODS: A total of 91 patients with upper limb HZ at the First Hospital of Jiaxing between January 2015 and August 2021 were enrolled. The patients were divided into mild, moderate, and severe HZ groups according to their numeric rating scale (NRS) scores. The occurrence of PHN was defined as a poor prognosis. The patients were divided into non-PHN and PHN groups according to the occurrence of PHN. Motor and sensory conduction indices of the median nerve were measured in each group. Spearman's correlation analysis was used to analyze the relationship between the EMG-related data of the median nerve and the NRS score and muscle strength. Univariate and multivariate logistic regression analyses were used to determine the independent influencing factors of PHN in patients with upper limb HZ, and the receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of EMG-related data in patients with upper limb HZ. RESULTS: Among 91 patients, there were 29 patients in the mild HZ group, 31 in the moderate HZ group, and 31 in the severe HZ group. The sensory nerve action potential (SNAP) amplitude of the median nerve in the severe and moderate HZ groups was lower than that in the mild HZ group, and that in the severe HZ group was lower than that in the moderate HZ group (F = 22.192, P < 0.05). Through Spearman's correlation analysis, it was found that the compound muscle action potential (CMAP) and SNAP amplitudes of the median nerve on the affected limb were negatively correlated with the NRS score (r = -0.266, P = 0.011; r = -0.778, P < 0.001), and there was no significant correlation between each index and muscle strength (P > 0.05). Among 91 patients, 44 and 47 were in the non-PHN and PHN groups, respectively. Univariate and multivariate logistic regression analyses showed that the CMAP amplitude of the median nerve on the affected limb (OR = 0.241, 95% CI: 0.098-0.567, P = 0.001) and SNAP amplitude (OR = 0.268, 95% CI: 0.110-0.628, P = 0.002) were independent influencing factors of PHN. Through the analysis of the ROC curve, it was found that the CMAP and SNAP amplitudes of the median nerve on the affected limb had a high predictive value for PHN (AUC = 0.657, P = 0.010; AUC = 0.773, P < 0.001). The cutoff values were 5.45 mV and 10.80 mV, respectively; and the predictive value of the 2 indices combined was the highest (AUC = 0.785, P < 0.001). LIMITATIONS: The nonrandomized, single-center, small sample size, and retrospective design are major limitations of this study. CONCLUSION: The CMAP and SNAP amplitudes of the median nerve on the affected limb were related to the degree of pain in patients with upper limb HZ. The CMAP and SNAP amplitudes of the median nerve on the affected limb can be used as prognostic factors for patients with upper limb HZ, and CMAP amplitude combined with SNAP amplitude is more valuable in predicting prognosis.

Comparison of Efficacy and Safety of Lumbar Sympathetic Radiofrequency Thermocoagulation Versus Chemical Lumbar Sympathectomy in the Treatment of Cold Hypersensitivity in the Hands and Feet: A Retrospective Study.

BACKGROUND: Cold hypersensitivity in the hands and feet (CHHF) is a disease characterized by abnormal cold in the limbs with limited treatment options. Compared to traditional drug therapy, lumbar sympathectomy is a new minimally invasive surgical method for treating CHHF. OBJECTIVES: The present study aimed to compare the efficacy and safety of lumbar sympathetic radiofrequency thermocoagulation (RFT) and chemical lumbar sympathectomy (CLS) in treating CHHF. STUDY DESIGN: A single-center, retrospective, observational study. SETTING: Department of Anesthesiology and Pain Medicine, Jiaxing, China. METHODS: A total of 102 patients with CHHF who underwent lumbar sympathectomy from January 2016 to April 2020 were included in this study. According to the mode of operation, the patients were divided into 2 groups: CLS (n = 56) and RFT (n = 46). All patients were treated under the guidance of computed tomography (CT). The foot temperature (T) and peripheral perfusion index (PI) were compared between the 2 groups before and after treatment. The 2 groups' visual analog scale (VAS) scores were evaluated before the operation and 1 day, 1 month, 3 months, 6 months, and 1 year after the treatment. The postoperative recurrence rate of the 2 groups was observed 1 year after treatment. The short and long-term complications during the postoperative follow-up were recorded. RESULTS: All patients completed the operation successfully. No significant difference was noted in the gender, age, course of the disease, preoperative T and PI, and postoperative T and PI between the 2 groups (P > 0.05). The postoperative T and PI were significantly increased compared to preoperative in both groups (P < 0.05). No significant difference was observed in T and PI between the 2 groups (P > 0.05), and no significant difference was recorded in VAS scores between the 2 groups 1 day and 1 month after the treatment (P > 0.05). The VAS scores at 3 months, 6 months, and 1 year after the treatment were significantly lower in the RFT group compared to the CLS group (P < 0.05). During the 1-year follow-up, patients who received CLS had a higher risk of recurrence than RFT treatment (P < 0.05). The RFT group treatment of CHHF showed better long-term outcomes than the CLS group. About 12.5% of patients in the CLS group and 6.5% in the RFT group had postoperative complications, including pain at the puncture site and genitofemoral neuralgia. However, no severe complications or deaths were observed in either of the 2 groups. LIMITATIONS: The was a single-center, retrospective, non-randomized study, which is a major limitation of this study. CONCLUSIONS: Lumbar sympathetic RFT had better long-term efficacy, lower recurrence, and fewer complications than the chemical lumbar sympathectomy when treating CHHF.

Evaluation of the efficacy of unipolar and bipolar spinal dorsal root ganglion radiofrequency thermocoagulation in the treatment of postherpetic neuralgia.

BACKGROUND: Different views have been proposed on the radiofrequency treatment modes and parameters of radiofrequency thermocoagulation of the spinal dorsal root ganglion for the treatment of postherpetic neuralgia (PHN). It is urgent to identify a more effective therapy for patients with PHN. METHODS: Patients who underwent radiofrequency thermocoagulation therapy for PHN were retrospectively reviewed and were divided into a radiofrequency thermocoagulation (CRF) and double neddles radiofrequency thermocoagulation (DCRF). The pain scores (numerical rating scale, NRS) were evaluated at the following time points: before the operation, 1 day, 3 months, 6 months, 1 year, and 2 years after operation. The incidence of complications and the degree of pain relief were evaluated. The in vitro ovalbumin experiment was used to indicate the effects of radiofrequency thermocoagulation. RESULTS: Compared with the preoperative NRS scores, the postoperative NRS scores decreased significantly; the NRS scores of the DCRF group was lower than that of the CRF group at all time points from 6 months to 2 years following the operation. The total effective rate of the DCRF group was significantly higher than that of the CRF group at 2 years following the operation. The incidence of numbness in the DCRF group was higher than that noted in the CRF group. The ovalbumin experiments in vitro indicated that the effects of radiofrequency thermocoagulation were optimal when the distance between the two needles was 5 mm. CONCLUSIONS: DCRF with a 5 mm spacing exhibits a longer duration and higher effective rate in the treatment of PHN and is worth promoting.

Risk Factors Affecting the Success Rate of Radiofrequency Thermocoagulation of Lumbar Sympathetic Nerve.

BACKGROUND: Computed tomography (CT)-guided radiofrequency thermocoagulation of lumbar sympathetic nerve has been gradually applied to the treatment of many autonomic nerve disorders, such as plantar hyperhidrosis (PH) and diabetic peripheral neuropathy (DPN). The difference in the success rate of operation between the left and right sides is not yet studied. OBJECTIVE: This study aimed to explore a statistically significant difference between the success rate of left and right CT-guided radiofrequency thermocoagulation of lumbar sympathetic nerve and screen the risk factors affecting the success rate of the right surgery. STUDY DESIGN: This is a single-center retrospective cohort study. SETTING: The study was carried out in the Pain Department of the affiliated Hospital of Jiaxing College in Jiaxing, China. METHODS: A total of 86 patients who received CT-guided radiofrequency thermocoagulation of lumbar sympathetic nerve were included in this study approved by the Ethics Committee of the affiliated Hospital of Jiaxing University. Nonparametric and chi-square tests were used to compare the operation times, CT scan times, and success rate on the left and right sides. Binary multivariate logistic regression analysis was applied to screen the risk factors on the outcome variable. RESULTS: The bilateral operation time, CT scan times, and success rate differed significantly between the left and right sides (P < 0.05). After univariate analysis, 6 covariates (gender, body mass index, treatment history, operation time, CT scan times, and puncture needle type) were selected. Finally, the multivariate regression model screened out 2 risk factors: the operation time and puncture needle type. LIMITATIONS: We look forward to increasing the sample size in follow-up studies and exploring relevant conclusions in randomized controlled trials. CONCLUSION: This study proved that in CT-guided radiofrequency thermocoagulation of the lumbar sympathetic nerve, the difficulty of operation on the right side was significantly high, and the success rate was also lower than that on the contralateral side. Multivariate logistic regression analysis showed that operation time and type of puncture needle were risk factors affecting the success rate of the operation. These findings laid a foundation for the accomplishment of technical improvement and innovation in the future. A preliminary exploration was carried out to reduce the risk and complications and to improve the success rate of the operation.

Rosiglitazone Alleviates Mechanical Allodynia of Rats with Bone Cancer Pain through the Activation of PPAR-γ to Inhibit the NF-κB/NLRP3 Inflammatory Axis in Spinal Cord Neurons.

Bone cancer pain (BCP) is a serious clinical problem that affects the quality of life of cancer patients. However, the current treatment methods for this condition are still unsatisfactory. This study investigated whether intrathecal injection of rosiglitazone modulates the noxious behaviors associated with BCP, and the possible mechanisms related to this effect were explored. We found that rosiglitazone treatment relieved bone cancer-induced mechanical hyperalgesia in a dose-dependent manner, promoted the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) in spinal cord neurons, and inhibited the activation of the nuclear factor-kappa B (NF-κB)/nod-like receptor protein 3 (NLRP3) inflammatory axis induced by BCP. However, concurrent administration of the PPAR-γ antagonist GW9662 reversed these effects. The results show that rosiglitazone inhibits the NF-κB/NLRP3 inflammation axis by activating PPAR-γ in spinal neurons, thereby alleviating BCP. Therefore, the PPAR-γ/NF-κB/NLRP3 signaling pathway may be a potential target for the treatment of BCP in the future.

Electroacupuncture Attenuates Cancer-Induced Bone Pain via NF-κB/CXCL12 Signaling in Midbrain Periaqueductal Gray.

Electroacupuncture (EA) is effective in various chronic pains. NF-κB and CXCL12 modulate the formation of chronic pain. Herein, we hypothesized that EA alleviates cancer-induced bone pain (CIBP) through NF-κB/CXCL12 axis in midbrain periaqueductal gray (PAG), which participates in "top-down" pain modulatory circuits. In order to filter the optimum EA frequency for CIBP treatment, 2, 100, or 2/100 Hz EA was set up. In addition, ipsilateral, contralateral, and bilateral EA groups were established to affirm the optimal EA scheme. Bilateral 2/100 Hz EA was considered as the optimal therapeutic scheme and was applied in a subsequent experiment. Western blotting along with immunofluorescence illustrated that CIBP induces a rapid and substantial increase in CXCL12 protein level and NF-κB phosphorylation in vlPAG from day 6 to day 12. Anti-CXCL12 neutralizing antibody and pAAV-U6-shRNA(CXCL12)-CMV-EGFP-WPRE in vlPAG remarkably improved the mechanical pain threshold of the hind paw in CIBP model relative to the control. EA inhibited the upregulation of pNF-κB and CXCL12 in vlPAG of CIBP. The recombinant CXCL12 and pAAV-CMV-CXCL12-EF1a-EGFP-3Xflag-WPRE reversed the abirritation of EA in the CIBP rat model. NF-κB phosphorylation mediated-CXCL12 expression contributed to CIBP allodynia, whereas EA suppressed NF-κB phosphorylation in CIBP. According to the above evidence, we conclude that bilateral 2/100 Hz EA is an optimal therapeutic scheme for CIBP. The abirritation mechanism of EA might reduce the expression of CXCL12 by inhibiting the activation of NF-κB, which might lead to the restraint of descending facilitation of CIBP.

CT-guided Chemical Lumbar Sympathectomy in the Treatment of Cold Hypersensitivity in the Hands and Feet.

BACKGROUND: Cold hypersensitivity in the hands and feet is a common clinical symptom in Asian women. Currently, treatment of cold hypersensitivity in the hands and feet is still limited to traditional Chinese medicine, mainly herbal medicine. However, many patients with cold hypersensitivity in the hands and feet in China are not satisfied with the therapeutic effect of herbal medicine, and took medication for a longer time. Chemical lumbar sympathectomy is widely used in the treatment of plantar hyperhidrosis, diabetic foot, recalcitrant erythromelalgia, and other diseases. OBJECTIVES: This study was conducted to evaluate the short-term as well as long-term efficacy, complications, and patient satisfaction of chemical lumbar sympathectomy during treatment cold hypersensitivity in the hands and feet. STUDY DESIGN: A retrospective, observational study. SETTING: Department of Anesthesiology and Pain Medicine, Jiaxing, China. METHODS: A retrospective study of 72 patients with cold hypersensitivity in the hands and feet who received chemical lumbar sympathectomy treatment in our hospital from January 2015 to October 2018 was conducted. The heart rate, non-invasive blood pressure, oxygen saturation, visual analog scale, perfusion index, and plantar temperature were monitored and recorded in before treatment (T1) and after treatment (T2) groups. The patients were followed up on day 1, at week 1, 1 month, 3 months, 6 months, one year, and 2 years after operation for satisfaction, complications, and recurrence. RESULTS: There were no significant differences in heart rate, non-invasive blood pressure, and oxygen saturation between T1 and T2 groups (P > 0.05). Perfusion index and plantar temperature in T2 group were remarkably higher than T1 group, and the difference was statistically significant (P < 0.01). The visual analog scale score of the T2 group was significantly reduced (P < 0.01). Of all the patients who underwent chemical lumbar sympathectomy, the postoperative therapeutic effect was effective in 63 cases (87.5%) and ineffective in 9 cases (12.5%). Among the effective patients, the postoperative curative effect was shown to be excellent in 47 cases and improved in 16 cases. According to the follow-up results at day 1, 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years after operation, the satisfaction rate was 87.5%, 87.5%, 81.9%, 61.1%, 52.7%, 41.6%, and 34.7%, respectively. There were no serious complications observed and 23 patients relapsed after two years. Multivariate logistic regression analysis results showed that the effect of visual analog scale (OR = 7.312, 95% CI: 1.598 - 33.646, P = 0.011) and plantar temperature (OR = 0.470, 95% CI: 0.288 - 0.766, P = 0.002) on therapeutic effect showed has statistical significance; the effect of gender (OR = 0.654, 95% CI: 0.134 - 3.181, P = 0.599), age (OR = 0.975, 95% CI: 0.916 - 1.039, P = 0.441), perfusion index (OR = 0.710, 95% CI: 0.367 - 1.375, P = 0.310), and disease course (OR = 1.019, 95% CI: 0.997 - 1.042, P = 0.088) on therapeutic effect showed no statistical significance. The effect of gender (OR = 0.451, 95% CI 0.131 - 1.554, P = 0.207), age (OR = 0.961, 95% CI 0.912 - 1.013, P = 0.141), and course of disease (OR = 1.006, 95% CI 0.997 - 1.015, P = 0.203) on postoperative recurrence showed no statistical significance. LIMITATIONS: The nonrandomized, single-center, small sample size, retrospective design is a major limitation of this study. CONCLUSIONS: Chemical lumbar sympathectomy is a valid treatment option for cold hypersensitivity in hands and feet, and computed tomography-guided percutaneous puncture chemical lumbar sympathectomy has the advantages of high success rate, less invasion, less complications, and repeatablity.

Spinal Nrf2 translocation may inhibit neuronal NF-κB activation and alleviate allodynia in a rat model of bone cancer pain.

Bone cancer pain (BCP) is a clinical pathology that urgently needs to be solved, but research on the mechanism of BCP has so far achieved limited success. Nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) has been shown to be involved in pain, but its involvement in BCP and the specific mechanism have yet to be examined. This study aimed to test the hypothesis that BCP induces the transfer of Nrf2 from the cytoplasm to the nucleus and further promotes nuclear transcription to activate heme oxygenase-1 (HO-1) and inhibit the activation of nuclear factor-kappa B (NF-κB) signalling, ultimately regulating the neuroinflammatory response. Von-Frey was used for behavioural analysis in rats with BCP, whereas western blotting, real-time quantitative PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect molecular expression changes, and immunofluorescence was used to detect cellular localization. We demonstrated that BCP induced increased Nrf2 nuclear protein expression with decreased cytoplasmic protein expression in the spinal cord. Further increases in Nrf2 nuclear protein expression can alleviate hyperalgesia and activate HO-1 to inhibit the expression of NF-κB nuclear protein and inflammatory factors. Strikingly, intrathecal administration of the corresponding siRNA reversed the above effects. In addition, the results of double immune labelling revealed that Nrf2 and NF-κB were coexpressed in spinal cord neurons of rats with BCP. In summary, these findings suggest that the entry of Nrf2 into the nucleus promotes the expression of HO-1, inhibiting activation of the NF-κB signalling pathway, reducing neuroinflammation and ultimately exerting an anti-nociceptive effect.

Pretreatment with Pectoral Nerve Block II Is Effective for Reducing Pain in Patients Undergoing Thoracoscopic Lobectomy: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Although video-assisted thoracoscopy has a smaller incision than traditional surgery, the postoperative pain is still severe. Ultrasound-guided pectoral nerve block (PECS) II is a new technique that can reduce pain in patients, and it had not been reported in the analgesia after thoracoscopic lobectomy. METHODS: 40 patients scheduled for thoracoscopic lobectomy were randomly divided into two groups. Patients in the PECS II group received 0.5% ropivacaine 25 ml before the general anesthesia, while patients in the placebo group received 0.9% saline. Thirty minutes after the block was performed, a pin-prick test was used to analyze the sense of pain of T2-T6 segments. The primary endpoint was the total consumption of fentanyl. Data were collected in the postanesthesia care unit (PACU) and in the ward within 24 hours after operation. RESULTS: The total consumption of fentanyl and the consumption of fentanyl in the intravenous analgesia pump within 24 hours after the operation were significantly lower in the PECS II group compared to the placebo group (p < 0.05). The implementation rate of rescue analgesia during operation and in PACU in the PECS II group was significantly lower than that in the placebo group (p < 0.05). The numerical rating scale (NRS) in 1 and 4 h after operation was lower in the PECS II group (p < 0.05). Mean arterial pressure (MAP) and heart rate (HR) of the PECS II group at chest entering (T1) were significantly lower than those in the placebo group (p < 0.05). CONCLUSION: Preconditioning of PECS II can stabilize the intraoperative circulation and significantly reduce pain and the consumption of opioids after operation.