Effectiveness and Safety of Flupentixol and Melitracen Tablets for the Treatment of Patients with Persistent Idiopathic Facial Pain: A Retrospective Observational Study.

BACKGROUND: Flupentixol and melitracen are being investigated for their potential effectiveness in managing persistent idiopathic facial pain (PIFP), based on their mechanisms of action as dopamine receptor antagonists and noradrenaline/serotonin reuptake inhibitors, respectively. The efficacy and safety of flupentixol and melitracen (FM) tablets in treating PIFP were retrospectively analyzed at our hospital. OBJECTIVES: The aim of this study is to determine the effectiveness and safety of FM tablets in treating PIFP. STUDY DESIGN: Retrospective unicentric cohort design. SETTING: An academic university hospital. METHODS: A retrospective analysis was conducted on a cohort comprising 128 patients with a definite diagnoses of PIFP who were treated with FM tablets (flupentixol 0.5 mg and melitracen 10 mg tablet, >= 4 tablets/d) from January 2022 through May 2023 at an academic university hospital. Baseline conditions were statistically described, and Numeric Rating Scale (NRS-11) scores of pain levels before and during treatment were collected. Pain relief rates were calculated. Differences in baseline characteristics between responsive and unresponsive patients were evaluated using statistical tests. Additionally, the side effects experienced during treatment were summarized. RESULTS: Among the included 128 patients, 105 (82.0%) patients achieved pain relief (pain NRS-11 score reduction rate >= 50%). The median treatment onset time was 3 (1-7) days. NRS-11 scores of responsive patients at week 2, week 4, week 8, and week 12 were significantly lower than the baseline NRS-11 scores (P < 0.001), regardless of their Hamilton Depression Rating Scale score. Pain duration was the only factor that related to responsiveness (Wilcoxon rank sum test, P < 0.001; logistic regression, P = 0.001). No serious side effects that could affect patients' lives were observed during the first week of treatments. LIMITATIONS: Due to its retrospective nature, this study is limited by its lack of a randomized control. The lack of data on nonresponders who did not achieve significant pain relief hinders assessing overall change and the placebo effects'. Patients previously treated with antidepressants were excluded, making it hard to determine if FM tablets were a better treatment for PIFP. Additionally, the small sample size in a single center may be influenced by chance variation in pain relief. CONCLUSIONS: FM tablets showed its potential in the management of PIFP with considerable efficacy and safety. Early administration of FM tablets after a PIFP diagnosis may result in a high possibility of pain relief.

Pre-emptive infiltration with betamethasone and ropivacaine for postoperative pain in laminoplasty and laminectomy (PRE-EASE): a prospective randomized controlled trial.

BACKGROUND: Postoperative pain after laminoplasty and laminectomy occurs partially from local trauma of the paraspinal tissue. Finding a multimodal analgesic cocktail to enhance the duration and effect of local infiltration analgesia is crucial. Because of the rapid onset and long duration of action of betamethasone, the authors hypothesized that, a pre-emptive multimodal infiltration regimen of betamethasone and ropivacaine reduces pain scores and opioid demand, and improves patient satisfaction following laminoplasty and laminectomy. MATERIALS AND METHODS: This prospective, randomized, open-label, blinded endpoint study was conducted between 1 September 2021 and 3 June 2022, and included patients between the ages of 18 and 64 scheduled for elective laminoplasty or laminectomy under general anesthesia, with American Society of Anesthesiologists classification I/II. One hundred sixteen patients were randomly assigned to either the BR (Betamethasone-Ropivacaine) group or the R (Ropivacaine) group in a 1:1 ratio. Each group received pre-emptive infiltration of a total of 10 ml study solution into each level. Every 30 ml of study solution composed of 0.5 ml of betamethasone plus 14.5 ml of saline and 15 ml of 1% ropivacaine for the BR group, and 15 ml of 1% ropivacaine added to 15 ml of saline for the R group. Infiltration of epidural space and intrathecal space were avoided and the spinous process, transverse process, facet joints, and lamina were injected, along with paravertebral muscles and subcutaneous tissue. Cumulative 48 h postoperative butorphanol consumption via PCA (Patient-controlled analgesia) was the primary outcome. Intention-to-treat (ITT) principle was used for primary analysis. RESULTS: Baseline characteristics were identical in both groups ( P >0.05). The cumulative 48 h postoperative butorphanol consumption via PCA was 3.0±1.4 mg in the BR group ( n =58), and 7.1±1.2 mg in the R group ( n =58) ( P <0.001). Overall cumulative opioid demand was lower at different time intervals in the BR group ( P <0.001), along with the estimated median time of first analgesia demand via PCA (3.3 h in the BR group and 1.6 h in the R group). The visual analog scale (VAS) score at movement and rest were also significantly lower until 3 months and 6 weeks, respectively. No side effects or adverse events associated with the intervention were observed in this study. CONCLUSIONS: Pre-emptive analgesia with betamethasone and ropivacaine provides better postoperative pain management following laminoplasty and laminectomy, compared to ropivacaine alone. This is an effective technique worthy of further evaluation.

PROCESS Trial: Effect of Duloxetine Premedication for Postherpetic Neuralgia Within 72 Hours of Herpes Zoster Reactivation-A Randomized Controlled Trial.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster (HZ) and results in severe refractory neuropathic pain. This study aimed at evaluating the efficacy of premedication with duloxetine in the prevention of PHN. METHODS: The PROCESS trial is a multicenter, randomized, open-label, blinded-endpoint trial used a 1:1 duloxetine:control ratio. Adults 50 years or older with HZ who presented with vesicles within 72 hours were recruited. The primary outcome was the incidence of PHN at 12 weeks. PHN was defined as any pain intensity score other than 0 mm on the visual analog scale (VAS) at week 12 after the onset of the rash. The secondary outcomes were the number of participants with VAS >0 and VAS ≥3. The modified intention-to-treat (mITT) principle and per-protocol (PP) principle were used for the primary outcome analysis. RESULTS: A total of 375 participants were randomly assigned to the duloxetine group and 375 were assigned to the control group. There was no significant difference in the incidence of PHN in the duloxetine group compared with the control group in the mITT analysis (86 [22.9%] of 375 vs 108 [28.8%] of 375; P = .067). PP analysis produced similar results. However, there were significant differences between the 2 groups in the number of participants with VAS >0 and VAS ≥3 (P < .05 for all comparisons). CONCLUSIONS: Although absolute prevention of PHN does not occur, this trial found that premedication with duloxetine can reduce pain associated with HZ, and therefore can have clinically relevant benefits. Clinical Trials Registration. Clinicaltrials.gov, NCT04313335. Registered on 18 March 2020.

Effectiveness and safety of high-voltage pulsed radiofrequency to treat patients with primary trigeminal neuralgia: a multicenter, randomized, double-blind, controlled study.

BACKGROUND: Trigeminal neuralgia (TN) is a debilitating pain disorder that still lacks an ideal treatment option. Pulsed radiofrequency (PRF), especially with high output voltage, is a novel and minimally invasive technique. PRF is regarded a promising treatment option for TN patients who respond poorly to medical treatment; however, the available evidence still lacks high quality randomized controlled trials (RCTs). Our study aimed to evaluate the long-term (1 year and 2 years) effects and safety of high-voltage PRF in primary TN patients and provide stronger evidence for TN treatment options. METHODS: We performed a multicenter, double-blind, RCT in adults (aged 18-75 years) with primary TN who responded poorly to drug therapy or were unable to tolerate the side effects of drug. Eligible participants were randomly assigned (1:1) to receive either high voltage PRF or nerve block with steroid and local anesthetic drugs. The primary endpoint was the 1-year response rate. This trial has been registered in the clinicaltrials.gov website (registration number: NCT03131466). RESULTS: One hundred and sixty-two patients were screened for enrollment between April 28th,2017 and September1st, 2019, among whom, 28 were excluded. One hundred and thirty-four participants were randomly assigned to either receive high voltage PRF (n = 67) or nerve block (n = 67). The proportion of patients with a positive response at 1-year after the procedure in the PRF group was significantly higher than that in the nerve block group in the intention-to-treat population (73.1% vs. 32.8%, p < 0.001). There was no difference between groups in the incidence of adverse events. CONCLUSIONS: Our findings support that high voltage PRF could be a preferred interventional choice prior to receiving more invasive surgical treatment or neuro-destructive treatment for TN patients who have poor responses to medical treatment. TRIAL REGISTRATION: Our study has been registered at ClinicalTrials.gov (trial registration number: NCT03131466).

Pre-emptive coinfiltration of dexamethasone palmitate emulsion with ropivacaine for postoperative pain in patients undergoing major spine surgery: a study protocol for a prospective, randomised controlled, multicentre trial.

INTRODUCTION: Patients undergoing major spine surgery usually experience moderate-to-severe postoperative pain. It has been shown that dexamethasone as an adjunct to local anaesthesia (LA) infiltration presented a superior analgesic benefit compared with LA alone in various types of surgeries. However, a recent meta-analysis reported that the overall benefits of dexamethasone infiltration were marginal. Dexamethasone palmitate (DXP) emulsion is a targeted liposteroid. Compared with dexamethasone, DXP has a stronger anti-inflammatory effect, longer duration of action and fewer adverse effects. We hypothesised that the additive analgesic effects of DXP on local incisional infiltration in major spine surgery may have better postoperative analgesic effect, compared with local anaesthetic alone. However, no study has evaluated this so far. The purpose of this trial is to determine whether pre-emptive coinfiltration of DXP emulsion and ropivacaine at surgical site incision will further reduce postoperative opioid requirements and pain scores after spine surgery than that with ropivacaine alone. METHODS AND ANALYSIS: This is a prospective, randomised, open-label, blinded endpoint, multicentre study. 124 patients scheduled for elective laminoplasty or laminectomy with no more than three levels will be randomly allocated in a 1:1 ratio into two groups: the intervention group will receive local incision site infiltration with ropivacaine plus DXP; the control group will receive infiltration with ropivacaine alone. All participants will complete a 3 months follow-up. The primary outcome will be the cumulative sufentanil consumption within 24 hours after surgery. The secondary outcomes will include further analgesia outcome assessments, steroid-related side effects and other complications, within the 3 months follow-up period. ETHICS AND DISSEMINATION: This study protocol has been approved by the Institutional Review Board of Beijing Tiantan Hospital (KY-2019-112-02-3). All participants will provide a written informed consent. The results will be submitted for publication in a peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05693467.

Methylprednisolone as an Adjunct to Local Infiltration on Laminoplasty or Laminectomy before Wound Closure: A Randomized Controlled Trial.

TrialDesign. Patients undergoing laminoplasty and laminectomy often experience severe postoperative pain. Local infiltration analgesia during spine surgery significantly reduces postoperative pain, which only upholds for a short time. Whether methylprednisolone and local anaesthetics are better than local anaesthetics alone in postoperative analgesia is yet to be determined. The primary aim of this research was the postoperative evaluation of efficacy and safety of methylprednisolone when used as an adjunct to local anaesthesia, ropivacaine, before wound closure after surgical procedures, laminoplasty or laminectomy. Methods. 132 patients were divided with a ratio of 1 : 1 into methylprednisolone-ropivacaine and ropivacaine alone groups. Every 30 ml of local infiltration solution consisted of 15 ml of 1% ropivacaine with 14 ml of saline along with 1 ml of 40 mg methylprednisolone and 15 ml of 1% ropivacaine with 15 ml of saline in methylprednisolone-ropivacaine group and ropivacaine group, respectively. The standardization of the study solution depended on the number of levels involved in surgery. Primary outcome was the 48-hour cumulative sufentanil demand. Results. Demographic characters and surgical variables among the groups were identical. The average 48-hour cumulative sufentanil demand was 32.5 ± 20.6 µg in the methylprednisolone-ropivacaine group and 50.9 ± 27.2 µg in the ropivacaine group (p < 0.001). The estimated median time of demand of the first analgesia via patient-controlled analgesia (PCA) pump was 2.5 hours and 2 hours in the methylprednisolone-ropivacaine group and the ropivacaine group, respectively (hazard ratio (HR) was 0.53, with 95% Cl 0.33 to 0.87 and Log-rank of p = 0.0019). Conclusion. The infiltration of methylprednisolone as adjunct ropivacaine before wound closure is a safe and efficient strategy for pain management following laminoplasty or laminectomy.

REDUCE trial: the effects of perineural dexamethasone on scalp nerve blocks for relief of postcraniotomy pain-a study protocol for a randomized controlled trial.

BACKGROUND: Pain is common in the first 2 days after major craniotomy. Inadequate analgesia may lead to an increased risk of postoperative complications. Most pain following craniotomy arises from the pericranial muscles and soft tissues of the scalp. Scalp nerve blocks with local anesthesia seem to provide effective, safe, however, transient postoperative analgesia which does not seem to meet the requirements of craniotomy. Currently, peripheral dexamethasone has been observed to significantly prolong the duration of analgesia of nerve blocks (e.g., saphenous nerve block, adductor canal block, thoracic paravertebral block, brachial plexus nerve block). On the contrary, a study reported that perineural dexamethasone did not appear to prolong the analgesic time after supratentorial craniotomy. However, all patients in this study were given 24 mg of oral or intravenous dexamethasone regularly for at least 7 days during the perioperative period, which possibly masked the role of single local low doses of perineural dexamethasone. Therefore, the analgesic effect of single dexamethasone for scalp nerve blocks without the background of perioperative glucocorticoid deserves further clarification. METHODS: The REDUCE trial is a prospective, single-center, parallel-group randomized controlled trial involving a total of 156 adults scheduled for elective craniotomy with general anesthesia. Patients will be randomly divided among two groups: the control group (n = 78) will receive scalp nerve blocks with 0.5% bupivacaine, plus normal saline with epinephrine at 1:200,000; the DEX4mg group (n = 78) will receive scalp nerve blocks with 0.5% bupivacaine, plus 4 mg dexamethasone with epinephrine at 1:200,000. The primary outcome will be the duration of analgesia, defined as the time between the performance of the block and the first analgesic request. DISCUSSION: The REDUCE trial aims to further assess the analgesic effect of single dexamethasone as an adjuvant to scalp nerve blocks for relief of postcraniotomy pain without the background of perioperative glucocorticoid. TRIAL REGISTRATION: ClinicalTrials.gov NCT04648358 . Registered on November 30, 2020.

The PATCH trial: efficacy and safety of 5% lidocaine-medicated plaster for the treatment of patients with trigeminal neuralgia: a study protocol for a multicentric, double-blind, enriched enrolment randomised withdrawal, vehicle-controlled study.

INTRODUCTION: Trigeminal neuralgia (TN) is characterised by a sudden, severe, electric shock like paroxysmal pain, which is almost always associated with triggers. Carbamazepine is the first-line medical management of TN. However, side effects are common. Currently, there is no ideal treatment for TN. Since there is a known abnormality of Na+ channels in the trigger zone, 5% lidocaine-medicated plaster (LMP), which can block the Na+ channels on Aδ and C fibres, is an effective treatment method in many chronic pain conditions. A case report has found the benefit of LMP for the treatment of TN without any side effects. Whether LMP is an option for the treatment of TN is worth exploring. METHODS AND ANALYSIS: The PATCH trial is a double-blind, enriched enrolment with randomised withdrawal, vehicle-controlled trial, aiming to explore the effects and safety of LMP in patients with TN. There is a 3-week initial open-label phase, followed by a 4-week double-blind treatment phase for responders. In the double-blind phase, patients will have to withdraw from this PATCH study if they meet one of the following criteria for treatment failure such as: >50% increase in pain intensity or paroxysms, lack of efficacy or side effects. The primary outcome will be the number of treatment failures. Adverse events will also be monitored throughout the study. ETHICS AND DISSEMINATION: This study protocol has been approved by the Institutional Review Board of Beijing Tiantan Hospital (approval number: KY 2020-102-02). The results will be disseminated in international academic meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04570293.

Dexamethasone as a ropivacaine adjuvant to pre-emptive incision-site infiltration analgesia in pediatric craniotomy patients: A prospective, multicenter, randomized, double-blind, controlled trial.

BACKGROUND: Dexamethasone added to incision-site infiltration has been routinely used to reduce pain after tonsillectomy in children. However, this has not been studied in pediatric craniotomy patients yet. We hypothesized that incision-site infiltration with a combination of ropivacaine and dexamethasone might provide superior analgesia to ropivacaine alone in pediatric craniotomy patients. METHODS: In this multicenter, double-blind, randomized, controlled trial, children aged 2-12 years, scheduled for craniotomy, were prospectively enrolled at two study centers, from September 2, 2019, to July 5, 2020. Eighty children were randomly assigned (1:1) to either ropivacaine plus dexamethasone group who received pre-emptive incision-site infiltration with 0.2% ropivacaine plus 0.025% dexamethasone, or ropivacaine group who received 0.2% ropivacaine alone. Primary outcome was the modified Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS) at 24 h postoperatively. Primary analysis was performed using the modified intention-to-treat principle. RESULTS: Pre-emptive incision-site infiltration with ropivacaine plus dexamethasone had a reduced pain score of 2.0, compared with the pain score of 2.9 in the ropivacaine group, at 24 h postoperatively (mean difference -0.9, 95% confidence interval [CI], -1.7 to -0.2; p = .019). Estimated median of the time of first rescue analgesic demand was 24 h in the ropivacaine plus dexamethasone group and 8.5 h in the ropivacaine group [hazard ratio 0.43, 95% CI 0.24 to 0.08; Log-rank p = .0025]. No adverse events related to incision-site infiltration with dexamethasone were observed in this study. DISCUSSION: Dexamethsone reduces the local production of pro-inflammatory factors after tissue damage and as a ropivacaine adjuvant for incision-site infiltration reduced the pain scores by 31% at 24 h postoperatively. The results were similar to several prior studies on to tonsillectomy patients. However, this changes on pain scores might has limited clinical significance. CONCLUSIONS: The addition of dexamethasone to ropivacaine for preoperative incision-site infiltration has better postoperative analgesic effect than ropivacaine alone in pediatric craniotomy patients.

Effect of duloxetine premedication for postherpetic neuralgia within 72 h of herpes zoster reactivation [PROCESS]: a study protocol for a randomized controlled trial.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common complication attributed to herpes zoster, which involves the reactivation of residual varicella zoster virus. It has been reported previously that pre-emptive amitriptyline following acute herpes zoster has shown latent positive effects in the prevention of PHN. In this study, by interfering with the same targets, norepinephrine and serotonin, we aim to evaluate whether pre-emptive duloxetine may proactively prevent PHN development. METHODS: This is a nationwide multicentric, randomized, open-label, blinded-endpoint study that will recruit 750 participants from 18 primary centres in China. Patients aged more than 50 years who are diagnosed with uncomplicated HZ, present with vesicles within 72 h of their emergence, and have an average pain score of at least 40/100 mm on a visual analogue scale (VAS, 0 mm = no pain, 100 mm = worst possible pain, at opposite ends of a 100-mm line) will be recruited for this study. Participants will be randomized into a duloxetine arm and a control arm. Participants allocated to the duloxetine arm will be given antivirals, analgesics and duloxetine, while those allocated to the control arm will receive antivirals and analgesics but no duloxetine. The primary outcome of this study is preventive efficacy against PHN, which will be evaluated based on a 100 mm VAS. Any pain scores other than 0 mm on the VAS 12 weeks after HZ onset will be defined as PHN. The secondary outcomes will consist of the average weekly VAS score, the average weekly consumption of each analgesic, weekly feature of the pain, patients' quality of life based on the 12-item Short-Form Health Survey, Patient Global Impression of Change Scale, sleep quality as evaluated by the Pittsburgh Sleep Quality Index and adverse events during the study period. DISCUSSION: This study will investigate a prophylactic approach for reducing the prevalence of postherpetic neuralgia with duloxetine and will add significant new knowledge on the preventive effects of duloxetine on PHN. TRIAL REGISTRATION: Clinicaltrials.gov NCT04313335 . Registered on 18 March 2020.

The Long-Term Outcome of CT-Guided Pulsed Radiofrequency in the Treatment of Idiopathic Glossopharyngeal Neuralgia: A Retrospective Multi-Center Case Series.

BACKGROUND: Safer and minimal invasive treatment options with minor side effects are in great demand in the treatment of glossopharyngeal neuralgia (GPN). Pulsed radiofrequency (PRF) is a micro-destructive procedure that could be applied repeatedly without irreversible damage to target tissue. However, few studies have reported the long-term clinical outcomes of PRF in the management of idiopathic GPN patients. METHODS: We retrospectively investigated the efficacy and safety of computed tomography (CT)-guided PRF in the treatment of 30 patients with idiopathic GPN in a multi-center clinical study. Numeric rating scale (NRS) score was used to evaluate pain intensity before and after PRF treatment. The effective rate was defined as the percentage of patients with NRS reduction of more than 50%. Baseline characteristics, surgical records, initial pain relief, time to take effect, long-term outcomes, patient satisfaction using a five-level Likert Scale, the incidence of recurrence as well as subsequent treatment choices, intraoperative and postoperative complications were retrieved from electronic medical records. RESULTS: A total of 30 idiopathic GPN patients who received PRF under CT-guidance were included in our study and the initial effective rate was 93.3%. The cumulative proportion of patients with satisfactory pain relief survival was 93.3% at 12 months, 89.6% at 24 months, 85.3% at 36 months, 79.6% at 48 months, 73.0% at 60 months and 72 months, and 54.8% at 84 months, 108 months as well as 120 months. No serious morbidity or mortality were observed in any of the cases. The median patient satisfaction in Likert scale rating was 4.0 (IQR, 3.0-5.0). CONCLUSION: According to our results, PRF is an effective and safe therapy for patients with idiopathic GPN. This minimally invasive, micro-destructive, neuro-modulatory technique could be a potential intervention of choice for the treatment of GPN patients who respond poorly to pharmacological treatment.

Preemptive Infiltration with Betamethasone and Ropivacaine for Postoperative Pain in Laminoplasty or Laminectomy (PRE-EASE): study protocol for a randomized controlled trial.

BACKGROUND: Laminoplasty and laminectomy have been used for decades for the treatment of intraspinal space-occupying lesions, spinal stenosis, disc herniation, injuries, etc. After these procedures, patients often experience severe postoperative pain at the surgical site. Intense immediate postoperative pain after many spinal procedures makes its control of utmost importance. Preemptive injection of local anesthetics can significantly reduce postoperative pain during rest and movement; however, the analgesic effect is only maintained for a relatively short period of time. Whether betamethasone combined with local anesthetic for laminoplasty or laminectomy has better short-term and long-term effects than the local anesthetic alone has not been reported yet. METHODS: The PRE-EASE trial is a prospective, randomized, open-label, blinded endpoint, single-center clinical study including 116 participants scheduled for elective laminoplasty or laminectomy, with a 6 months' follow-up process. Preemptive local infiltration with betamethasone and ropivacaine (treatment group) or ropivacaine alone (control group) throughout the entire thickness of the planned incision site will be performed by the surgeon prior to making the incision. The primary outcome will be the cumulative butorphanol consumption within the first 48-h postoperative period. DISCUSSION: This study will add significant new knowledge to the effect and feasibility of preemptive local infiltration of betamethasone for postoperative pain management in laminoplasty and laminectomy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04153396. Registered on 6 November 2019.