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1.
J Pain Res ; 17: 3241-3253, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39371492

RESUMO

Objective: This study aimed to evaluate the prognostic accuracy of the Current Perception Threshold (CPT) in Acute Herpetic Neuralgia (AHN) patients receiving Pulsed Radiofrequency (PRF) therapy and to develop a corresponding prognostic model. Methods: We retrospectively analyzed data from 106 AHN patients treated with PRF between January 2022 and May 2023. The occurrence of Postherpetic Neuralgia (PHN) after treatment categorized patients into non-PHN and PHN groups. The predictive role of CPT indices for PRF outcomes was assessed using the Receiver Operating Characteristic (ROC) curve and Area Under Curve (AUC). Then the dataset was split into a training set (n=74) and a validation set (n=32). Factors associated with PHN development were identified using univariate and multivariate logistic regression. A nomogram model was developed using significant predictors and internal validation was performed using valid set data. Results: Among the 106 patients, 45 had a poor prognosis. Significant differences in age, preoperative Numerical Rating Scale (NRS) score, and 5Hz CPT ratio were observed between the groups (p<0.05). Logistic regression identified these factors as independent predictors for PRF prognosis (p<0.05). The 5Hz CPT ratio demonstrated predictive value (AUC= 0.764, 95% CI: 0.674-0.855). The nomogram model, incorporating these predictors, showed high AUC in both the training (0.863, 95% CI: 0.776-0.950) and validation sets (0.859, 95% CI: 0.721-0.998). Calibration curves indicated good model fit, and the Hosmer-Lemeshow test confirmed this (p>0.05). Decision Curve Analysis (DCA) highlighted the model's predictive advantage. Conclusion: The 5Hz CPT ratio can predict the prognosis of PRF in AHN patients. The nomogram model has high precision and clinical utility. It can help identify AHN patients with a poor PRF prognosis at an early stage and assist in clinical decision-making.

2.
Neuropharmacology ; 261: 110164, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39307393

RESUMO

The management and treatment of bone cancer pain (BCP) remain significant clinical challenges, imposing substantial economic burdens on patients and society. Extensive research has demonstrated that BCP induces changes in the gene expression of peripheral sensory nerves and neurons, which play crucial roles in the onset and maintenance of BCP. However, our understanding of the epigenetic mechanisms of BCP underlying the transcriptional regulation of pro-nociceptive (such as inflammatory factors and the transient receptor potential family) and anti-nociceptive (such as potassium channels and opioid receptors) genes remains limited. This article reviews the epigenetic regulatory mechanisms in BCP, analyzing the roles of histone modifications, DNA methylation, and noncoding RNAs (ncRNAs) in the expression of pro-nociceptive and anti-nociceptive genes. Finally, we provide a comprehensive view of the functional mechanisms of epigenetic regulation in BCP and explore the potential of these epigenetic molecules as therapeutic targets for BCP.

3.
Eur J Pharmacol ; 970: 176480, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38490468

RESUMO

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.


Assuntos
Neoplasias Ósseas , Dor do Câncer , Curcumina , Ratos , Animais , Dor do Câncer/tratamento farmacológico , Dor do Câncer/metabolismo , Curcumina/farmacologia , Curcumina/uso terapêutico , Curcumina/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sensibilização do Sistema Nervoso Central , Quinase I-kappa B/metabolismo , Dor/tratamento farmacológico , Neoplasias Ósseas/complicações , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Analgésicos/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Medula Espinal , Potássio/metabolismo
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