Pain and Therapy最新文献

Introduction: This study integrated structural magnetic resonance imaging (sMRI) of the brain with clinical characteristics to identify the "vulnerable brain regions" and risk factors associated with the development of postherpetic neuralgia (PHN) in patients with acute and subacute herpetic neuralgia. Furthermore, the study explored the combined predictive performance of these neuroimaging and clinical indicators.

Methods: From February 2023 to January 2025, a total of 214 hospitalized patients with acute and subacute herpetic neuralgia were enrolled. Follow-up was conducted via telephone or outpatient visits, revealing that 116 patients (54.98%) developed PHN, while 95 did not. Clinical data and magnetic resonance imaging (MRI) data were collected for all participants. T1-weighted structural MRI images underwent preprocessing procedures including N4 bias field correction, skull stripping, brain tissue segmentation, and parcellation. Gray matter volume (GMV) values were extracted from 90 predefined regions of interest (ROIs) for further analysis. Group differences were assessed using two-tailed Student's t-tests or the non-parametric Kruskal-Wallis H test, as appropriate. Features showing significant intergroup differences in GMV were integrated with clinical variables to train machine learning models, and receiver-operating characteristic (ROC) curve analysis was employed to evaluate their predictive performance for PHN.

Results: Significant differences were observed between the PHN and Non-PHN groups in several clinical variables, including age, body mass index (BMI), age ≥ 50 years, disease duration, admission Numeric Rating Scale (NRS) score, hospitalization during the acute phase (< 1 month), involved dermatome, and total Charlson Comorbidity Index (CCI) score (all P < 0.05). In terms of neuroimaging findings, GMV differed significantly between the two groups in the following brain regions: the left inferior frontal gyrus (triangular part), fusiform gyrus, Heschl's gyrus, and superior temporal gyrus; the right orbital part of the inferior frontal gyrus, lentiform nucleus (globus pallidus); and the bilateral cingulate gyrus, hippocampus, and caudate nucleus (P < 0.05, corrected for multiple comparisons using the false discovery rate [FDR] method). The combined model integrating T1-weighted MRI features and clinical characteristics achieved an area under the ROC curve (AUC) of 0.748 (95% CI 0.677-0.816) for predicting the occurrence of PHN.

Conclusion: This study is the first to innovatively integrate sMRI to identify "vulnerable brain regions" associated with the transition from acute and subacute herpetic neuralgia to PHN. By combining GMV metrics with clinical features, the study provides a novel approach for predicting the development of PHN.

Introduction: Randomized controlled trials have established onabotulinumtoxinA as an effective prophylactic treatment for chronic migraine. However, real-world evidence in the Saudi population remains limited. This study aimed to evaluate the clinical effectiveness of onabotulinumtoxinA injections in patients with chronic migraine treated at a tertiary care center in Jeddah, Saudi Arabia between 2016 and 2024.

Methods: A retrospective analysis was conducted at King Abdulaziz Medical City in Jeddah, Saudi Arabia. Migraine Disability Assessment Test (MIDAS) was used. Data on patients' demographics, number of onabotulinumtoxinA doses (155 U for each dose), pain level, days of headache in the 3 months following the last injection, and side effects experienced after each injection session were gathered.

Results: Among 133 patients studied, 85% were female, 56.4% were aged ≤ 40 years, and 66.9% had ≤ 14 headache days in the 3 months following the last injection. The median MIDAS score decreased from 28 (severe disability) to 8 (mild disability). Median headache days were reduced from 60 to 10 days. Patients with MIDAS Grade I had a significant higher number of onabotulinumtoxinA doses. A significant negative correlation was found between number of onabotulinumtoxinA doses and the MIDAS grade, pain level, and days of headache in the 3 months post injection. Side effects were experienced by 13.5% of patients, with ptosis being the most common.

Conclusion: OnabotulinumtoxinA resulted in meaningful reductions in migraine-related disability, headache frequency, and pain intensity in patients with chronic migraine treated in a tertiary care center. These findings reinforce its role as an effective long-term preventive therapy and highlight the importance of maintaining consistent treatment cycles to sustain clinical benefit.

Introduction: Postoperative pain after surgery for colorectal cancer (CRC) is prone to multiple complications, and opioids are accompanied by significant side effects. There is still unclear evidence regarding the combination of esketamine and lidocaine. This trial was designed to get into the bottom of the synergistic effect of esketamine and lidocaine on reducing opioid requirements in the elderly undergoing CRC surgery.

Methods: This study enrolled 151 patients to establish the control group (group C, n = 50), the esketamine group (group S, n = 50), and the esketamine + lidocaine group (group SL, n = 51). The primary endpoint was the total sufentanil consumption within 24 h post-surgery.

Results: During the first 24 h postoperatively, compared with group C {103.22 μg (103.22 morphine milligram equivalents [MME]), 98.30-108.25 μg}, both group S (100.29 μg [100.29 MME], 99.60-104.43 μg) and group SL (95.13 μg [95.13 MME], 95.20-100.40 μg) had reduced dosage of sufentanil (mean, interquartile range [IQR]) (P < 0.001); while at the remaining time points, groups S/SL were also lower than group C (P < 0.05). The numeric rating scale (NRS) pain scores in the two postoperative days were lower in groups S/SL than in group C, even lower in group SL than group S (P < 0.001). The intraoperative heart rate and mean blood pressure were more likely to be elevated in group S than in group C, while it was lower in group SL than in group S (P < 0.05). Group SL had an accelerated recovery of gastrointestinal function and higher subjective postoperative recovery quality scores on the third and seventh postoperative days than group C (P < 0.05), as well as lower rate of postoperative nausea and vomiting (P = 0.022).

Conclusions: Esketamine combined with lidocaine may reduce opioid consumption, improve postoperative analgesia, and better maintain hemodynamic stability during CRC surgery in elderly patients.

Trial registration information: Chinese Clinical Trial Registry (registration no. ChiCTR2300078997; registration date: 22 December 2023).

Introduction: Pudendal neuralgia (PN) is a chronic neuropathic pain syndrome affecting the pudendal nerve, often presenting with perineal or pelvic pain exacerbated by sitting. The aim of this systematic review was to summarize the existing knowledge on the diagnosis and management of PN.

Methods: A PubMed database search identified 475 articles, of which 35 met the inclusion criteria. Nine studies focused on diagnostic strategies, and 26 on management.

Results: Diagnosis of PN is largely clinical, with the Nantes criteria providing a widely adopted framework. Imaging modalities such as MRI and MR neurography, along with neurophysiological tests including quantitative sensory testing, have been explored as adjuncts, though their roles remain limited. Pudendal nerve blocks are both diagnostic and therapeutic, with response rates up to 94%. Management follows a stepwise approach, beginning with conservative therapies and progressing to nerve blocks, and extending to neuromodulation or surgery when necessary. Pulsed radiofrequency and nerve stimulation techniques demonstrate promising results, with reported pain reduction in up to 95% of refractory cases, though long-term durability remains uncertain. Surgical decompression remains the most common operative option, with several techniques described.

Conclusions: Despite the established recognition of PN, there is a paucity of high-quality comparative studies and randomized controlled trials assessing diagnostic accuracy and treatment efficacy. Current evidence suggests conservative measures and nerve blocks are sufficient for most patients, with stimulation techniques and decompression surgery reserved for refractory cases. Emerging modalities may offer future therapeutic options, but require validation in larger cohorts.

Introduction: Prescriptions of transmucosal immediate-release fentanyl (TIRF) have increased in recent years, driven by their rapid onset and ease of administration compared to other opioids like morphine and oxycodone, especially for breakthrough pain. A 2022 study reported high rates of off-label TIRF use, particularly among general practitioners (GPs). This study aimed to assess the prevalence and patterns of off-label TIRF use by GPs, and perceived efficacy for predictable pain associated with medical procedures. Secondary objectives included evaluating its use in other specific contexts such as swallowing or alertness disorders, acute pain, and overall tolerability.

Methods: A mixed-methods study was designed to combine qualitative interviews exploring clinical contexts with a quantitative cross-sectional survey assessing the prevalence of off-label use of TIRF among French GPs. Data were collected through a national online survey.

Results: A total of 682 completed questionnaires were analyzed. The study focused exclusively on off-label prescribing of TIRFs. Off-label use was reported by 46% of GPs across a variety of clinical indications. Specifically, 244 GPs (36%; 95% CI 32-40) reported prescribing TIRFs for procedural pain. Other off-label indications were also reported, including use for alertness disorders (24%; 95% CI 21-27), swallowing disorders (32%; 95% CI 28-35), and acute rheumatological pain (12%; 95% CI 9-14). These findings highlight a substantial level of off-label prescribing, with varying perceptions of efficacy and tolerability across different clinical contexts.

Conclusions: This study confirms widespread off-label TIRF use in well-defined clinical situations. While many GPs report positive outcomes, important concerns remain, including limited training, difficulty with dose titration, and the risk of use disorder. Targeted education and clearer prescribing guidelines could help ensure a safer and more appropriate use of TIRF in GPs practice.

Introduction: Effective postoperative pain management is crucial for patient recovery and satisfaction. Smoking may impact pain perception and analgesic requirements, but its effects on postoperative opioid needs remain unclear. The objective of this study was to determine whether patients who smoke have different postoperative opioid requirements compared to nonsmokers in the first 24 and 48 h after surgery.

Methods: We conducted a systematic review and meta-analysis of studies comparing postoperative opioid use between smokers and nonsmokers. A comprehensive literature search was performed in Web of Science and PubMed databases. Opioid doses were converted to morphine equivalents for comparison. Random effects meta-analysis was used to calculate pooled effect sizes.

Results: Eight studies (784 patients) were included for the primary 24-h outcome and seven studies (1164 patients) for the 48-h outcome. Meta-analysis showed significantly higher opioid requirements in smokers compared to nonsmokers at both 24 h (standardized mean difference [SMD] 0.90, 95% CI 0.74-1.06, p < 0.00001) and 48 h postoperatively (SMD 0.61, 95% CI 0.48-0.74, p < 0.00001). On average, smokers required 33.7% more opioids than nonsmokers. Smokers also reported significantly higher pain scores 24 h after surgery (SMD 0.59, 95% CI 0.26-0.92, p < 0.001).

Conclusions: Despite low-quality evidence due to non-randomized study designs, this meta-analysis demonstrates that patients who smoke have significantly higher postoperative opioid requirements and pain scores than nonsmokers. These findings highlight the need to consider smoking status when developing postoperative pain management strategies. Further research is needed to elucidate the mechanisms underlying this relationship and optimize pain control in smokers.

Introduction: The sacral erector spinae plane (S-ESP) block is a recently described regional anesthesia technique that targets sacral dermatomes. First reported in 2019, it has been increasingly explored as a potential option for perioperative analgesia in surgeries involving the sacral, perineal, and pelvic regions. This review aims to summarize and critically appraise the current anatomical, technical, and clinical evidence on the S-ESP block, outlining its mechanisms of action, approaches, efficacy, and safety while identifying research gaps and future directions.

Methods: We performed a narrative review integrating anatomical descriptions, sonographic techniques, and available randomized controlled trials (RCTs) evaluating the clinical efficacy of the S-ESP block. A comprehensive literature search was conducted in PubMed, Embase, Scopus, Web of Science, and Ovid (Medline) from inception to July 21, 2025, without language or date restrictions. Full-text RCTs investigating ultrasound-guided S-ESP blocks for perioperative analgesia were reviewed and summarized.

Results: Fourteen RCTs (published 2023-2025) were included, conducted predominantly in Turkey, India, and Egypt, spanning pediatric (6 months to 12 years) and adult populations undergoing circumcision, hypospadias repair, hemorrhoidectomy, pilonidal sinus surgery, transurethral resection of prostate, lumbar discectomy, and total hip arthroplasty. Most pediatric trials compared midline S-ESP with caudal or penile blocks, generally demonstrating a longer time to first rescue analgesia and reduced postoperative analgesic consumption, although one study reported a superior duration with caudal block. In adults, the S-ESP block consistently reduced pain scores and opioid requirements.

Conclusions: Current evidence suggests that both midline and paramedian S-ESP techniques are technically feasible, appear safe in the short term, and provide clinically relevant postoperative analgesia in selected pediatric urogenital, adult anorectal, and orthopedic surgeries. However, heterogeneity in techniques, small single-center samples, and a narrow range of indications limit its generalizability. Large, multicenter RCTs with standardized protocols are needed to clarify the optimal approaches, dosing strategies, and comparative role of S-ESP block versus established neuraxial and peripheral techniques.

Post-stroke pain (PSP) and post-stroke depression (PSD) represent two major neuropsychiatric complications that frequently co-occur, with comorbidity rates ranging from 34 to 65.6%. Despite their high prevalence and profound impact on functional recovery and quality of life, the shared mechanisms and optimal management of this complex comorbidity remain poorly understood. We conducted a systematic review of clinical and preclinical evidence to explore the epidemiological characteristics, diagnostic challenges, neurobiological underpinnings, and therapeutic strategies for comorbid PSP and PSD. Special emphasis was placed on neuroinflammatory cascades, glial cell dysfunction, monoaminergic system dysregulation, and maladaptive neural circuit remodeling. We found PSP and PSD exhibit overlapping pathophysiological mechanisms, including microglial activation, astrocytic reactivity, pro-inflammatory cytokine release (e.g., TNF-α, IL-1β, IL-6), and dysregulation of cortico-limbic circuits involving the anterior cingulate cortex, amygdala, and ventral tegmental area. Pharmacotherapies such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and NMDA receptor antagonists (e.g., ketamine), as well as neuromodulation approaches (e.g., repetitive transcranial magnetic stimulation [rTMS], transcranial direct current stimulation [tDCS]), demonstrate efficacy in both conditions, likely through anti-inflammatory and neural circuit-modulating effects. We speculate that the comorbidity of PSP and PSD is underpinned by convergent neuroimmune and neural circuit mechanisms. Targeting these shared pathways-such as with cytokine inhibitors, glial modulators, and circuit-specific neuromodulation-holds promise for developing integrated, mechanism-based therapies. Future research should prioritize multimodal treatment strategies tailored to the neurobiological signatures of this debilitating post-stroke syndrome. Infographic available for this article.

Introduction: This study aimed to assess changes in patient-reported outcomes during open-label acute treatment of migraine with zavegepant for up to 52 weeks.

Methods: Data were from a phase 2/3, open-label, long-term safety study of zavegepant for the acute treatment of migraine. Participants with migraine treated migraine attacks of any intensity as needed with one dose of zavegepant 10 mg nasal spray, up to once per day and up to eight times per 28 days, for up to 52 weeks. Pre-specified exploratory endpoints included change in number of migraine days/month, change in Migraine Disability Assessment (MIDAS) Scale, change in Migraine-Specific Quality of Life version 2.1 (MSQ v2.1), and Satisfaction with Medication.

Results: A total of 603 treated participants were analyzed. Zavegepant treatment was associated with mean reductions of 1.7 migraine days/month of any pain intensity and 1.1 migraine days/month of moderate or severe pain intensity. Zavegepant treatment was associated with improvement in mean MIDAS total score of - 8.2 (95% CI - 9.89, - 6.55) at week 12 and - 8.8 (95% CI - 11.13, - 6.50) at week 52. At week 12 and week 52, respectively, zavegepant treatment was associated with improvements in mean MSQ Role Function Restrictive domain score of 8.6 (95% CI 7.09, 10.16) and 13.8 (95% CI 11.76, 15.85), improvement in Role Function Preventive domain score of 6.7 (95% CI 5.25, 8.11) and 10.1 (95% CI 8.08, 12.13), and improvement in Emotional Function domain score of 6.8 (95% CI 4.87, 8.72) and 11.3 (95% CI 8.99, 13.70). At week 52, 44.2% (125/283) of participants were completely or very satisfied with zavegepant and 28.6% (81/283) were somewhat satisfied; 124 participants did not complete the Satisfaction with Medication scale at week 52.

Conclusion: Through the 52-week study, acute treatment with zavegepant was associated with reduction in mean number of migraine days/month, improvements in migraine-related disability and migraine-specific quality of life, and high levels of patient satisfaction.

Trial registration: ClinicalTrials.gov identifier NCT04408794.

Introduction: Axial pain is a common complication following expansive unilateral open-door laminoplasty (ELAP); however, traditional statistical methods are unable to effectively predict this complication. This study developed machine learning (ML) models to predict post-ELAP axial pain and identify key predictors.

Methods: This retrospective study enrolled 851 cervical spondylotic myelopathy (CSM) patients undergoing ELAP, split into training (n = 714) and temporal validation sets (n = 137). Demographic, imaging, clinical, and surgical data were collected. Predictive features were selected by the least absolute shrinkage and selection operator (Lasso) regression, followed by ML model development with grid search optimizing hyperparameters. The top-performing model underwent temporal validation, and SHapley Additive exPlanations (SHAP) analyzed predictor contributions.

Results: The training set included 218 axial pain cases; the test set had 47. Key predictors (C7 laminoplasty, cervical kyphosis, etc.) were identified to develop ML model. Post-optimization, extreme gradient boosting (XGBoost) achieved superior performance (internal validation area under the receiver [AUC] = 0.948; 95% confidence interval [CI] 0.918-0.978), maintained in temporal validation (AUC = 0.906; 95% CI 0.858-0.954). Through SHAP analysis, the predictors were ranked in descending order of importance as follows: C7 laminoplasty, quantity-based surgical segment classification, cervical kyphosis, angle of lamina open-door, cervical lordosis, and occupying rate of cervical spinal canal.

Conclusions: ML models coupled with SHAP analysis effectively predict post-ELAP axial pain, identifying the key predictors. Performing segment-selective ELAP, avoiding unnecessary C7 laminoplasty, and maintaining optimal open-door angle are critical factors in avoiding the occurrence of axial pain following ELAP.