Introduction: Herpes zoster (HZ) can adversely influence patients' quality of life and sometimes it can develop postherpetic neuralgia (PHN). To date, it remains challenging manage well using currently available therapies. Tender point infiltration (TPI) might have the potential to be an analgesic therapy for acute and subacute HZ pain. However, current evidence remains insufficient. Therefore, the purpose of this protocol is to design a study to: 1) evaluate the analgesia efficacy and safety of TPI for acute and subacute HZ; 2) to explore the positive predictors of TPI for prevention of PHN. Methods and Analysis: This study is designed as a randomized, prospective, multicenter, blinded endpoint, open-label controlled trial including a 12-month follow-up period. 176 qualified participants will be randomly split into the standard group or TPI group in a ratio of 1:1. Primary outcome will be the presence of PHN 12 months posttreatment. Secondary outcomes include the presence of PHN at month 3 and month 6 posttreatment. Visual Analogue Scales (VAS) for assessment of pain, consumption of oral analgesia drugs, patient satisfaction scores on the 5-point Likert scale, patients' quality of life scored on the WHOQOL-BREF at day 1, week 2, month 1, month 3, month 6 and month 12, proportion of patients receiving repeated TPIs and block points each time for TPI group. Multivariable logistic analyses will be performed to identify predictive factors for the prevention of PHN at month 12 after treatment. Safety evaluation will be determined by adverse events during the trial.

Xiangjun Zhou,1 Rong Han,2 Zhigang Zhao,2 Fang Luo1 1Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of ChinaCorrespondence: Fang Luo, Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China, Tel +86 010 59976664, Email 13611326978@163.com

BACKGROUND:Previous studies on serotonin and norepinephrine reuptake inhibitors (SNRIs) such as duloxetine and venlafaxine have demonstrated efficacy in treating persistent idiopathic dentoalveolar pain (PIDP). However, a third-generation SNRI with favorable tolerability remains understudied in treating PIDP. The study aims to investigate the role of desvenlafaxine in improving PIDP. METHODS:Clinical data for patients diagnosed with PIDP who received desvenlafaxine treatment (50-150 mg per day) from March 2024 to January 2025 were retrospectively reviewed at our hospital. Through systematic review of electronic medical records, we extracted demographic and baseline pain characteristics, along with the effectiveness and safety of desvenlafaxine during a 3-month follow-up assessed by the Numeric Rating Scale-11 (NRS-11) scores for pain and adverse effects. Binary logistic regression was used to identify predictors of response. RESULTS:Among 103 patients, pain relief was achieved in 90 patients (87.4%), as evidenced by a ≥ 50% reduction in NRS-11 scores (p < 0.001), while the remaining 13 patients (12.6%) discontinued medications due to insufficient therapeutic efficacy. Binary logistic regression analysis identified shorter pain duration as an independent predictor of a favorable response to desvenlafaxine, with an odds ratio of 1.037 (95% CI = 1.016-1.058, p < 0.001). Adverse events were reported in 15 patients (14.6%), all mild and transient. CONCLUSIONS:The administration of desvenlafaxine serves as an effective and safe therapeutic approach for patients with PIDP. Patients with a short history of PIDP are more likely to benefit from desvenlafaxine treatment.

OBJECTIVES:To explore the association of stellate ganglion block with platelet-rich plasma plus lidocaine with clinical outcomes in adults with chronic migraine, in comparison to lidocaine alone. METHODS:This multicenter prospective exploratory study enrolled 200 adults with chronic migraine scheduled for stellate ganglion block across three hospitals from October 2024 to September 2025. Treatment allocation was based on patient preference within a prespecified quota design, with 100 patients per group receiving either platelet-rich plasma plus lidocaine or lidocaine alone. Propensity score matching was performed to balance confounders. The primary outcome was the mean change from baseline in monthly headache days at 1 month post-intervention. Secondary outcomes included headache frequency, pain intensity, headache duration, response rate, analgesic consumption, functional status, and safety. RESULTS:After propensity score matching, 66 patients per group were analyzed. At one month, the platelet-rich plasma plus lidocaine group showed a significantly greater reduction in monthly headache days compared with lidocaine alone (mean difference, 1.84 days; 95% confidence interval [CI], 0.68-2.99; p = 0.002). This advantage persisted at two and three months. The combination group also demonstrated superior improvements in pain intensity, headache duration, response rate, and analgesic reduction at all time points, along with better functional status at 1 and 2 months (all nominal P < 0.05). Baseline disability was a negative predictor of one-month response. No significant differences in safety outcomes were observed. CONCLUSION:In this exploratory study, stellate ganglion block with platelet-rich plasma plus lidocaine was associated with clinically meaningful improvements in headache outcomes and functional status compared with lidocaine alone in patients with chronic migraine, with a favorable safety profile. These findings warrant validation in a definitive randomized trial.

Background:The global prevalence of fibromyalgia (FM) in the general population is estimated to range from 2% to 4%. Pregabalin, a gamma-aminobutyric acid (GABA) analogue, is one of the most widely prescribed medications for FM. However, at therapeutic doses, its limited efficacy and/or unacceptable side effects mean that many patients derive only partial benefit, often leading to treatment discontinuation. Cyclobenzaprine is a centrally acting muscle relaxant. In August 2025, the United States Food and Drug Administration approved a sublingual formulation of cyclobenzaprine hydrochloride for treating FM in adults. However, its availability is largely confined to North America. Tizanidine, like cyclobenzaprine, is also a muscle relaxant with a central mechanism; however, there is no codified posology for FM treatment with tizanidine. Methods:This study aims to recruit 164 adult patients diagnosed with FM. Participants will be randomly assigned in a 1:1 ratio to either the intervention group (pregabalin plus tizanidine) or the control group (pregabalin monotherapy). The primary outcome is the change from baseline to week 12 in average pain intensity (during the last 7 days) assessed using the first item of the symptom domain of the Revised Fibromyalgia Impact Questionnaire (FIQR). Secondary outcomes, assessed at weeks 4, 8, 12, 16, 20, and 24, will include: widespread pain, symptom severity, functional performance, balance, muscle strength and power, psychological functioning, sleep quality, self-efficacy, treatment durability, and health-related quality of life. Ethics and Trial Registration:This study was approved by the Institutional Review Board of Beijing Tiantan Hospital (KY2025-217-03-08) and was registered with ClinicalTrials.gov (NCT07382921). All study procedures will be conducted in accordance with the Declaration of Helsinki (1964) and its subsequent amendments (7th revision, Fortaleza, Brazil, 2013). Conclusion:This trial will provide evidence for the efficacy and safety of pregabalin combined with tizanidine in the treatment of FM.

Background:Effective postoperative pain management remains a clinical challenge, with a substantial proportion of patients experiencing moderate to severe pain after surgery. Intravenous patient-controlled analgesia (PCA) is widely used; however, conventional fixed-rate basal infusion does not account for the dynamic temporal pattern of postoperative pain, potentially leading to suboptimal analgesia and unnecessary opioid exposure. Time-programmed decremental infusion has been proposed as an alternative strategy to better align opioid delivery with postoperative pain trajectories, but high-quality evidence in mixed surgical populations is limited. Methods and Analysis:This study is a prospective, multicenter, randomized, double-blind controlled trial conducted across three tertiary hospitals. A total of 1444 adult patients undergoing elective thoracic, abdominal, spinal, and orthopaedic procedures performed using either minimally invasive or open approaches will be randomized in a 1:1 ratio to receive either time-programmed decremental infusion or fixed-rate basal infusion PCA. All patients will receive a standardized PCA solution containing sufentanil 200 μg and ondansetron 32 mg diluted to 200 mL. The control group will receive a constant background infusion of 2 mL/h, whereas the intervention group will receive a predefined decremental infusion schedule (4.0, 3.0, 2.0, and 1.0 mL/h across successive postoperative time intervals). The primary outcome is cumulative opioid consumption at 48 hours postoperatively. Secondary outcomes include pain intensity, cumulative PCA volume, bolus demand frequency, rescue analgesic use, quality of recovery, sleep quality, sedation level, incidence of nausea and vomiting, and patient satisfaction. Analyses will be performed on the intention-to-treat and per-protocol populations. Ethics and Dissemination:The study protocol has been approved by the institutional review boards of all participating centers. The trial will be conducted in accordance with the Declaration of Helsinki, and written informed consent will be obtained from all participants. The findings will be disseminated through peer-reviewed journals and academic conferences. Trial Registration:Clinical Trials.gov identifier: NCT07375121. Registered on January, 2026. (https://clinicaltrials.gov/study/NCT07375121?term=NCT07375121&viewType=Card&rank=1).

INTRODUCTION:Inadequately managed postoperative pain remains a significant clinical challenge, often leading to delayed mobilisation and increased complications. While intravenous patient-controlled analgesia (PCA) is a mainstay of treatment, conventional fixed-rate basal infusion modes may not align with the fluctuating biphasic nature of postoperative pain. This often results in either insufficient analgesia or unnecessary opioid overexposure. Advanced network-integrated PCA pumps now allow for 'variable-rate feedback infusion,' which dynamically adjusts the background rate based on real-time patient demand. This study aims to determine whether a variable-rate feedback infusion mode reduces total cumulative opioid consumption at 48 hours postoperatively while providing non-inferior analgesic efficacy compared with a fixed-rate basal infusion mode. METHODS AND ANALYSIS:This is a multicentre, randomised, double-blind, controlled trial to be conducted at three hospitals in China. A total of 1170 patients (aged 18-65 years, American Society of Anaesthesiologists I-III) undergoing elective mixed surgery under general anaesthesia, including thoracic, abdominal, spinal, orthopaedic and cranial procedures performed using either minimally invasive or open approaches, will be recruited and randomised in a 1:1 ratio to either the fixed-rate basal infusion group or the variable-rate feedback infusion group. Both groups will receive a standardised PCA solution of sufentanil. In the variable-rate feedback infusion group, the background infusion rate will automatically increase by 0.5 mL/hour on demand boluses during lockout intervals and decrease by 0.5 mL/hour after 1 hour of inactivity. The primary outcome is the total cumulative opioid consumption at 48 hours postoperatively, including sufentanil delivered via PCA and opioid-equivalent rescue analgesics. Key secondary outcomes include resting and movement pain scores, cumulative PCA volume consumption, number and dosage of additional rescue analgesia and postoperative quality of recovery. Exploratory outcomes include sleep quality, sedation and agitation levels, and the degree of nausea and vomiting, patient's satisfaction with PCA. These outcomes are assessed at predefined postoperative time points. ETHICS AND DISSEMINATION:The study has been approved by the Institutional Review Board of Beijing Tiantan Hospital (KY2025-387-02) and the Affiliated Hospital of Youjiang Medical University for Nationalities (YYFY-LL-2026-006), and the Second Affiliated Hospital of Hainan Medical University (2026-K140-01). The study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent will be obtained from all participants before enrolment. Findings from this study will be disseminated through peer-reviewed journals and at scientific conferences. A summary of the findings will also be made available to participants on request. TRIAL REGISTRATION NUMBER:NCT07361822.

Background:Fibromyalgia (FM) is a chronic pain syndrome with limited response and delayed onset to current treatments. Esketamine (ESK) shows potential as a rapid-acting analgesic in FM patients, but previous low-dose studies have had limited efficacy and are constrained by single-center designs, monotherapy approaches, and small sample sizes. The efficacy of higher-dose ESK administered as an adjunct to guideline-recommended pharmacotherapy in FM remains unclear. Study Design:Multicenter, prospective, randomized, controlled, open-label, blinded-endpoint trial. Methods and Analysis:A total of 92 adult FM patients will be randomized in a 1:1 ratio to either the treatment group (single intravenous infusion of ESK plus oral pregabalin and venlafaxine) or the control group (oral pregabalin and venlafaxine alone). In the treatment group, ESK will be administered as a single intravenous infusion at a dose of 1 mg/kg on the day of enrollment. Both groups will follow identical dose titration regimens for pregabalin and venlafaxine, with dose escalation individualized according to patient tolerability and clinical response. Plasma concentrations of ESK and its metabolites will be measured at the end of infusion to enable a limited characterization of systemic exposure and to support exploratory exposure-response analyses. Participants will be followed for 12 weeks. The primary outcome is the change from baseline in the mean pain intensity during the first week after treatment. The secondary outcomes include average pain intensity, worst pain intensity, and proportion of patients achieving ≥50% and ≥30% pain reduction, median pain relief time, maximal tolerated doses of pregabalin and venlafaxine, patient-reported outcomes (Revised FM Impact Questionnaire, Hospital Anxiety and Depression Scale, Short Form 36 Health survey, Multidimensional Fatigue Inventory, and Medical Outcomes Study Sleep Scale), plasma concentrations of ESK and its metabolites at the end of infusion, and adverse events throughout the study period. Trial Registration:ClinicalTrails.gov identifier: NCT07230171. Registered on November 13, 2025 (https://www.clinicaltrials.gov/search?term=NCT07230171).

Background:Fibromyalgia (FM) is a chronic condition, imposing a substantial burden on patients. Pregabalin, a first-line treatment, offers incomplete efficacy for many and is associated with dose-limiting central nervous system adverse effects. Crisugabalin is a novel α2δ ligand with 23-fold higher binding affinity than pregabalin and has shown potentially fewer central nervous system adverse effects in animal models. While crisugabalin has shown efficacy in other neuropathic pain conditions, its efficacy in FM, particularly in a direct comparison with pregabalin, remains unclear. Methods and Analysis:This multicenter, prospective, randomized, pregabalin-controlled, open-label, blinded-endpoint study will be conducted at 10 hospitals in China. A total of 1116 adult patients with FM and a baseline average daily pain intensity of ≥4 on an 11-point numerical rating scale will be enrolled. Participants will be randomly assigned (1:1) to receive either crisugabalin or pregabalin for 12 weeks using a standardized, flexible-titration protocol. While participants and treating physicians will be aware of the treatment allocation, outcome assessors and data analysts will remain blinded. The primary outcome is the proportion of patients achieving at least a 50% reduction in average pain intensity from baseline at week 12. Secondary outcomes include pain intensity measures, study drug dosing and rescue analgesic utilization, Revised FM Impact Questionnaire, Brief Pain Inventory severity and interfere subscales, short-form 36 Health Survey, Patient Global Impression of Change Scale, Medical Outcomes Study Sleep Scale, Beck Depression Inventory-II, and incidence of adverse events. Analyses will be performed on the modified intention-to-treat and per-protocol populations. Ethics and Dissemination:This study, approved by the Institutional Review Board of Beijing Tiantan Hospital, Capital Medical University (KY2025-217-03), will be conducted in accordance with the Declaration of Helsinki. Written informed consent will be obtained from all participants, and findings will be disseminated through peer-reviewed publications and scientific conferences. Trial Registration:Clinical Trials.gov identifier: NCT07196657. Registered on September 29, 2025 (https://www.clinicaltrials.gov/search?term=NCT07196657).

BACKGROUND:Fibromyalgia (FM) is a chronic condition characterized by widespread pain and a range of somatic and psychological symptoms that impose a substantial burden on patients. While pregabalin is an approved and effective monotherapy for many individuals with FM, the efficacy of this medication is often incomplete, particularly for symptoms like fatigue and anxiety. Combination therapy incorporating selective serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine, has shown promise for enhancing therapeutic outcomes. Venlafaxine, an SNRI with demonstrated efficacy as an FM treatment, has a distinct pharmacological mechanism from pregabalin. However, the synergistic potential of pregabalin and venlafaxine in combination has not been formally evaluated. OBJECTIVES:This study protocol describes a trial designed to test the hypothesis that the combination of pregabalin and venlafaxine is superior to pregabalin monotherapy in providing pain relief to patients with FM. STUDY DESIGN:This is a multicenter, prospective, randomized, open-label, blinded-endpoint study. SETTING:This study will be conducted at 7 different hospitals. METHODS:We will recruit 750 adults with a diagnosis of FM and moderate-to-severe pain. Patients will be randomly assigned in a one-to-one ratio to receive either pregabalin monotherapy or combination therapy consisting of pregabalin and venlafaxine for 12 weeks. Both groups will follow a flexible, forced-titration schedule to achieve the maximum tolerated dose. While the patients and treating physicians will be aware of the treatment allocation, the outcome assessors will remain blinded. RESULTS:The primary outcome is the mean daily pain intensity at week 4, measured on an 11-point numeric rating scale. Secondary outcomes will be evaluated at baseline and at weeks one, 2, 4, 8, and 12 after the treatment initiation. Secondary outcomes include the worst pain intensity, the responder rates (≥ 30% and ≥ 50% pain reduction), the dose of pregabalin and/or venlafaxine, the Revised FM Impact Questionnaire, the Brief Pain Inventory severity and interference subscales, the 36-Item Short Form Survey (SF-36), the Medical Outcomes Study Sleep Scale, the Beck Depression Inventory-II, and adverse events (AEs) occuring throughout the study. Statistical analyses will be performed on the modified intention-to-treat population. LIMITATIONS:An open-label design will be employed, with patient follow-up limited to 12 weeks. CONCLUSION:If the combination of pregabalin and venlafaxine proves to be more effective and better tolerated than pregabalin monotherapy, the combination therapy could establish a new standard of care for FM patients who struggle to achieve sufficient pain relief through nonpharmacological therapies.

Background:Local anesthetic incision-site infiltration (ISI) effectively eases post-craniotomy pain; however, its short duration limits sustained analgesia. This study aimed to assess the efficacy and safety of ropivacaine combined with triamcinolone acetonide along with ropivacaine alone via ISI to manage postoperative pain in adult craniotomy patients. Methods:This prospective, randomized, open-label, controlled trial enrolled 110 patients (aged 18~65 years; American Society of Anesthesiologists Physical Status, I~III) scheduled for elective craniotomies. Patients were randomly allocated to two distinct groups: the treatment group received 0.5% ropivacaine combined with triamcinolone acetonide for ISI (n = 55) and the control group received 0.5% ropivacaine alone (n = 55). The primary outcome was sufentanil consumption (μg) via patient-controlled analgesia (PCA) within 48 h post-surgery using the intention-to-treat (ITT) principle and per-protocol (PP) analyses. Results:Within 48 hours post-surgery, the treatment group showed significantly lower cumulative sufentanil consumption than control group (8.4 ± 5.2 μg vs 32.7 ± 12.2 μg; mean difference: -24.3, 95% confidence interval -27.8 to -20.7; p < 0.001). The estimated median time to the first PCA-administered administration was 30 h in the treatment group versus 12 h in the control group (hazard ratio: 0.11, 95% CI: 0.07 to 0.18; log-rank p < 0.0001). A statistically significant decrease in numerical rating scale (NRS) pain scores was observed in the treatment group compared with the control group at all postoperative time points (2h to 1 month; p < 0.001 for all comparisons). No adverse events (AEs) occurred in either group during the study period. Conclusion:Compared with ropivacaine alone, the addition of triamcinolone acetonide for ISI was associated with improved postoperative analgesia and reduced sufentanil consumption in adults who underwent craniotomy. Moreover, the combination was linked to a lower incidence of postoperative nausea and vomiting (PONV), with no reported severe AEs.

Background Patients with insomnia may exhibit altered pharmacodynamics to anesthetics. This study aimed to explore the changes in propofol dosage in patients with insomnia undergoing digestive endoscopy, compared to patients with normal sleep patterns. Methods A multicenter prospective cohort study was conducted. Propensity score matching (1:3) was applied to balance baseline characteristics. The primary outcome was the total propofol consumption during digestive endoscopy, and gender/age/BMI subgroup analysis was performed. The secondary outcome included the propofol dosage required for successful endoscopic insertion and gender/age/BMI subgroup analysis, the recovery time, the correlation between propofol dosage requirements and insomnia severity, as well as perioperative adverse events. Results After matching (140 patients in the insomnia group vs 420 patients in the normal sleep group), the insomnia group required significantly higher total propofol consumption (3.8 ± 0.8 vs 3.3 ± 0.6 mg/kg, P = 0.003) and propofol dosage required for successful endoscopic insertion (2.4 ± 0.3 vs 2.1 ± 0.3 mg/kg, P = 0.043). Subgroup analyses of total propofol consumption and propofol dosage required for successful endoscopic insertion confirmed these findings across gender and age. The recovery time and the incidence of perioperative adverse events were comparable in both groups. A positive correlation was observed between propofol dosage and insomnia severity (P < 0.001). Conclusions Patients with insomnia require higher propofol dosages during digestive endoscopy, suggesting the need for individualized anesthesia protocols in this population. Trial registration: ClinicalTrials.Gov (NCT06376760, Principal investigator: Fang Luo, Date of registration: 17 April, 2024)

Introduction Fibromyalgia (FM) is a prevalent chronic pain condition that significantly impairs quality of life. The current treatments for FM still have some disadvantages and limitations. Pregabalin, a standard pharmacological treatment, provides relief for some patients but is associated with dose-dependent adverse events (AEs) and incomplete efficacy, highlighting a significant unmet clinical need. Mirogabalin, as a novel α2δ ligand similar to pregabalin but with distinct binding properties, has shown a favourable safety profile and potential analgesic effects in preclinical studies and trials for other neuropathic pain conditions. However, data on its efficacy in FM are limited and no studies have directly compared mirogabalin with pregabalin in an Asian FM population.Methods and analysis This is a prospective, multicentre, randomised, open-label, blinded endpoint trial to compare the efficacy and safety of mirogabalin versus pregabalin for the management of pain and other core symptoms in adult patients with FM. This study will be conducted at the Department of Pain Management, Beijing Tiantan Hospital, the First Affiliated Hospital of Nanchang University, Chongqing University Three Gorges Hospital, the First Affiliated Hospital of Army Medical University and the Affiliated Hospital of Yanbian University. Patients aged over 18 years, diagnosed with FM according to the 2016 Revisions to the 2010/2011 FM diagnostic criteria, will be enrolled. 674 qualified patients experiencing moderate-to-severe FM will be randomly assigned to either the pregabalin group or the mirogabalin group in a 1:1 ratio. Treatment will involve individualised dose titration based on treatment response and tolerability. All participants will be followed for a duration of 12 weeks. The primary outcome will be the proportion of patients achieving a pain reduction of at least 50% at 12 weeks. Secondary endpoints will include the average pain intensity, the worst pain intensity, the Revised FM Impact Questionnaire, the Brief Pain Inventory severity and interference subscales, the Short-Form 36 Health Survey, the Medical Outcomes Study Sleep Scale, the Beck Depression Inventory-II, AEs throughout the study. An open-label administration is selected to reflect real-world clinical practice and to allow individualised dose titration according to tolerability and response, while blinded endpoint assessment is implemented to minimise evaluation bias and preserve methodological rigour.Ethics and dissemination This study was approved by the Institutional Review Board of Beijing Tiantan Hospital, Capital Medical University (KY2025-217-03), the First Affiliated Hospital of Nanchang University (IIT (2026) Clinical Ethics Review no. 676), Chongqing University Three Gorges Hospital (2026 Scientific Ethics Review no. 41), the Affiliated Hospital of Yanbian University (Yan Medical Ethics no. 20260275) and the First Affiliated Hospital of Army Medical University (AIIT2026081KX). All participants will provide written informed consent prior to enrolment. This study will be conducted in accordance with the Declaration of Helsinki. Findings from this study will be disseminated through peer-reviewed journals and at scientific conferences.Trial registration number NCT07157852.

Introduction Postoperative pain is particularly pronounced in spinal surgery. Inadequate management of acute postoperative pain not only reduces patient satisfaction and delays recovery but also increases the risk of developing chronic pain. Local infiltration analgesia (LIA) is a widely used technique for perioperative pain management. However, even with the use of long-acting local anaesthetics, such as ropivacaine, postoperative analgesia often remains insufficient. Preliminary evidence suggests that combining diprospan, a mixture of betamethasone disodium phosphate and betamethasone dipropionate, with ropivacaine can significantly reduce analgesic requirements in the immediate postoperative period. However, concerns about steroid-related complications, including hyperglycaemia and surgical site infections, highlight the need to identify the minimum diprospan concentration to achieve a balance between efficacy and safety. This randomised, controlled, evaluator-blinded trial aims to investigate the dose-response relationship of diprospan as an adjunct to ropivacaine for LIA in spinal surgery to determine the minimum effective dose for effective and safe pain management.Methods and analysis This is a single-centre, randomised, evaluator-blinded, controlled, dose-mapping study in which subjects will be randomised in a 1:1:1:1:1 ratio to the control group or to receive diprospan at concentrations of 0.003%, 0.006%, 0.009% or 0.012%. Patients will receive either 0.5% ropivacaine alone or a corresponding dose of diprospan combined with 0.5% ropivacaine for LIA. All participants will be followed for a duration of 3 months. The primary outcome measure will be cumulative sufentanil consumption within the first 48 hours postsurgery. Secondary outcomes will include additional assessments of analgesia, steroid-related adverse events and other complications within the 3-month follow-up period.Ethics and dissemination This study protocol was approved by the Institutional Review Board of Beijing Tiantan Hospital (KY2024-365-02-1). Written informed consent will be obtained from all participants. The results will be submitted for publication in a peer-reviewed journal.Trial registration number NCT06785350.

The dysregulation of the microglia-neuron axis plays a pivotal role in the pathogenesis of cognitive dysfunction following traumatic brain injury (TBI). The C-C chemokine receptor 5 (CCR5), markedly upregulated on both microglia and neurons post-injury, serves as a crucial mediator in the neuroinflammatory response and consequent neurological deficits. However, the therapeutic application of CCR5 antagonists in TBI is impeded by the delivery barriers presented by the blood-brain barrier (BBB) and their limited neuron-targeting efficacy. In this study, we introduce a novel nasal-to-brain delivery nanoplatform designed to facilitate the efficient brain delivery of DAPTA, a peptide antagonist of CCR5, aiming to inhibit CCR5 signaling and improving cognitive function following TBI. Biocompatible chitosan nanocarriers grafted with cell-penetrating peptide (TAT) and neuron-binding lactoferrin (Lf) were initially fabricated, demonstrating substantial DAPTA loading capacity, active mucosal and neural transportation, and enhanced neuron-targeting capabilities. The dual-engineered nanodrugs (DA@LT NPs) effectively penetrated the trigeminal and olfactory nerves, significantly enhancing the transport of DAPTA into the brain following intranasal delivery. In a TBI-induced mouse model, DA@LT NPs markedly alleviated the neuroinflammatory response, promoted M2 microglia polarization, protected neurons from pyroptosis, and improved both motor and cognitive functions of animals. The non-invasive intranasal delivery of the therapeutic CCR5 peptide antagonist using these mucus-penetrating and neuron-targeting nanoformulations presents a promising intervention for ameliorating neurological inflammation and cognitive impairments associated with TBI.

INTRODUCTION:As a disorder of gut-brain interaction, irritable bowel syndrome (IBS) is a common reason for patient visits in primary and specialist care settings. IBS is associated with recurrent abdominal pain, altered bowel habit, resulting in alternating constipation and diarrhoea, bloating, without serious organic diseases. The bidirectional relationship between IBS and psychological factor is also complex. Studies have suggested that tricyclic antidepressants can effectively control the concomitant symptoms of IBS, especially some severe and refractory symptoms. At present, the conventional treatment of IBS remains somewhat unsatisfactory. Studies have shown that the antidepressant effects of esketamine are rapid and significant, whether a single low dose of esketamine is effective in IBS deserves further investigation. In this study, we hypothesise that a single low dose of esketamine will be effective for IBS. METHODS AND ANALYSIS:This is a single-centre, randomised, double-blind, placebo-controlled trial. Patients with IBS are divided into three levels according to the severity of IBS: mild, moderate and severe. 92 patients in the esketamine group and 92 patients in the control group who are scheduled for colonoscopy will be prospectively recruited in each level. The primary outcome is the IBS Severity Scoring System at baseline and at 3 days, 1 week, 3 weeks, 6 weeks after colonoscopy. The secondary outcome includes IBS-Quality of Life, Bristol Stool Form scale, Hospital Anxiety and Depression Scale, Patient Health Questionnaire-12 Somatic Symptom Score and adverse events. The allocation sequence is assigned by a random number table using a block randomisation method by SPSS (Version 26, IBM Inc., USA) Statistics software. All enrolled patients, anaesthesiologist B and researchers responsible for follow-up and data collection and analysis are therefore fully blinded. All data will be performed using SPSS Statistics software, and a p value <0.05 will be considered statistically significant. ETHICS AND DISSEMINATION:The protocol has been approved by the Medical Ethics Committee of Beijing Tiantan Hospital affiliated to Capital Medical University (KY2024-414-02). All participants will sign a written informed consent form. The results will be submitted for publication in peer-reviewed journals, presented at international conferences, and shared with participants via hospital newsletters. TRIAL REGISTRATION NUMBER:Efficacy of Esketamine for Patients With Irritable Bowel Syndrome (NCT06788444).

Traumatic brain injury (TBI) triggers complex neurovascular unit (NVU) damage via ischemia, reactive oxygen species (ROS) accumulation, and persistent immune activation, contributing to long-term neurological deficits. However, effective NVU repair remains challenging due to the multifactorial nature of secondary injury. Here, a novel multimodal nanotherapeutic platform designed to concurrently target multiple key pathological events underlying NVU disruption is presented. This nanodrug integrates ultrasmall cerium oxide nanoparticles and IRAK-4 siRNA within a ROS-responsive poly(1,4-phenyleneacetone dimethylene thioketal) (PPADT) matrix, cloaked with neutrophil membranes for inflammation homing. At the injury lesion, the responsive nature enables on-demand drug release, eliciting synergistic therapeutic actions. Specifically, the cerium nanodots catalyze ROS scavenging and oxygen generation, alleviating oxidative stress and hypoxia to facilitate blood-brain barrier restoration, pericyte repair, and improved cerebral perfusion. Simultaneously, IRAK-4 siRNA downregulates pro-inflammatory signaling and reprograms microglia toward an anti-inflammatory phenotype. In a murine TBI model, the nanotherapy promotes vascular repair, reduces brain edema, attenuates neuroinflammation, and preserves neuronal integrity. Additionally, treatment ameliorates sleep spindle loss, reduces epileptiform activity, and significantly improves cognitive performance in learning and memory tasks. This work highlights a multipronged therapeutic strategy capable of restoring NVU homeostasis and mitigating secondary brain injury, offering great promise for advancing TBI treatment.

BACKGROUND:Trigeminal neuralgia (TN) is one of the severest and most common forms of neuropathic pain, and the current standard treatments for TN still have some disadvantages and limitations. Pulsed radiofrequency (PRF) has great potential as a micro-destructive method in treating refractory TN, but the long-term outcomes of PRF have been reported to be unsatisfactory. Autologous platelet-rich plasma (PRP) can reduce inflammation and promote nerve repair and has been proven effective in a previously published case report. So far, there have been no reports on combining PRF with PRP for the treatment of TN. OBJECTIVE:We plan to conduct an open-label cohort study to compare the efficacy of PRF to that of PRF with PRP when each is applied to the Gasserian ganglion for the treatment of TN. STUDY DESIGN:A study protocol for a multicentric, prospective, observational, propensity score matching (PSM), parallel, cohort, non-randomized, and assessor-blinded trial. SETTING:Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University in Beijing, China; Department of Pain Management, Henan Provincial People's Hospital, Henan, China; Department of Pain Management, Huadong Hospital, Fudan University, Shanghai. METHODS:A total of 270 patients with idiopathic TN will be assigned equally to one of 2 groups, based on their willingness. Both groups will receive 2 Hz of PRF, with the PRP group also receiving 2 mL of leukocyte-poor platelet-rich plasma (LP-PRP) mixture, which will be injected slowly into the Gasserian ganglion and the mandibular nerve. It is estimated that 81 patients who receive the combination of PRF and PRP will be matched with 81 PRF-alone controls after a propensity score match (PSM) to ensure balanced comparisons between the 2 groups. RESULTS:The primary outcome will be the response rate of the treatment after 12 months, which is the percentage of patients with a modified Barrow Neurological Institute (BNI) pain intensity score between I and III. The secondary outcome will include the following: BNI score, Numeric Rating Scale score, dose of carbamazepine, patient satisfaction score, score on the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF), and adverse reactions. These data will be recorded over a one-year follow-up period. LIMITATIONS:The open-label study design may influence the measurement of outcomes and introduce bias, such as performance or ascertainment bias. CONCLUSIONS:To our knowledge, this trial will be the first multi-centric, prospective, observational study that has a relatively large sample size and compares the efficacy and safety of applied PRF to that of combined PRF and PRP for patients who have not responded to pharmacologic treatments for idiopathic TN. If the combination PRF-and-PRP treatment is proven effective, it will be an important, safe, minimally destructive alternative treatment modality for idiopathic TN that persists after ineffective conservative treatment.

OBJECTIVE:Pulsed radiofrequency (PRF) combined with low-temperature continuous radiofrequency (CRF) might be a novel technique for relieving trigeminal neuralgia (TN). This study aimed to evaluate the efficacy and safety of high-voltage PRF combined with low-temperature CRF in primary TN. METHODS:This randomized controlled trial was performed between December 2, 2020, and October 26, 2022. Eligible patients with TN were randomly assigned at a 1:1 ratio to receive either PRF with a voltage of 70 V at 42°C for 600 seconds followed by CRF at 60°C for 270 seconds (PRF+CRF group) or PRF with a voltage of 70 V at 42°C for 600 seconds (PRF group). The primary outcome was the response rate to treatment after 12 months. The secondary outcomes were the proportion of responders at 1 day, 1 week, 2 weeks, 1 month, 2 months, 3 months, and 6 months following the procedure and the 11-point numeric rating scale (NRS) scores at 1 day, 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, and 12 months following the procedure. Adverse events associated with surgery were also observed. RESULTS:A total of 169 patients with TN were screened, and 146 patients were randomized. The groups were well balanced across baseline characteristics. The percentage of responders at 12 months after surgery was significantly greater in the PRF+CRF group compared with the PRF group (83.6% [61/73] vs 67.1% [49/73], risk ratio 1.2 [95% CI 1.0-1.5], absolute difference 16.5%; p = 0.021). There was a higher proportion of responders after 1 day, 1 week, 2 weeks, 1 month, 2 months, 3 months, and 6 months (ratio difference 16.5%, 35.6%, 16.4%, 12.3%, 12.3%, 12.3%, and 15.1%, respectively; all p < 0.05). Moreover, lower NRS scores were observed in the PRF+CRF group at 1 day, 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, and 12 months following the procedure (all p < 0.05). Postoperative facial numbness scores were higher in the PRF+CRF group at 1 day, 1 week, 2 weeks, 1 month, and 2 months (all p < 0.05). Overall, 5.5% of patients in the PRF+CRF group and no patients in the PRF group reported masseter muscle weakening. No other complications, such as anesthesia dolorosa and corneal anesthesia, were observed in either group. CONCLUSIONS:High-voltage PRF combined with low-temperature (60°C) CRF could provide a significant improvement compared with high-voltage PRF alone. Clinical trial registration no.: NCT04174443 (ClinicalTrials.gov).