Pancreatic cancer is a devastating disease with less than 5% 5-year survival. Inoperable patients often present with pain. Randomized controlled trial have shown that endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) improves pain control. It is usually performed by injecting bupivacaine followed by absolute alcohol around the celiac axis.Single center, randomized, double blind controlled trial of EUS-CPN with and without bupivacaine in patients with inoperable malignancy (pancreatic or other) involving the celiac plexus. The study was approved by research ethics board with approval number of 2022-9969, 21.151 and registered on ClinicalTrials.gov (NCT04951804).We hypothesize that bupivacaine is superfluous and may actually reduce pain control by diluting the neurolytic effect of alcohol. Bupivacaine is also potentially dangerous in that it may produce serious adverse events such as arrythmias and cardiac arrest if inadvertently injected intravascularly.This randomized trial is designed to assess whether bupivacaine is of any value during EUS-CPN.The online version contains supplementary material available at 10.1186/s13063-023-07487-7. Pancreatic cancer is the most devastating of all cancers with a dismal survival rate. Pancreatic cancer is the 3rd most common cause of cancer-related deaths worldwide. The 5-year survival rate of all patients with pancreatic cancer is approximately 5%, and this figure has remained relatively stable over the past 25 years, since most patients present with inoperable disease , 2.Seventy to 80% of patients with pancreatic cancer have abdominal pain at the time of diagnosis, which reduces quality of life and possibly survivability. Adequate pain control is therefore considered an essential component for the care of these patients. In the initial phase, the pain is visceral, but with disease progression, somatic pain may occur, especially due to the peri-pancreatic invasion of neural structures, such as the celiac plexus .The effectiveness of CPN is well established. It is safe, produces significant pain reduction, significantly reduces narcotic requirements, and may even increase survivability –6. Wyse Currently, it is standard EUS-CPN practice to inject bupivacaine immediately before injecting absolute alcohol, to theoretically prevent pain during and after the procedure . HoweverIn our institution, we stopped applying bupivacaine during EUS-CPN approximately 2 years ago, with no obvious difference intra- or post-procedure and a possible reduction in the need for repeat neurolysis—suggesting that neurolysis without bupivacaine may be more effective (unpublished observations).Therefore, we designed a randomized clinical trial to determine if bupivacaine is of any value during EUS-CPN.The primary hypothesis for this study is that bupivacaine injection before neurolysis dilutes the neurolytic effect of alcohol and therefore decreases its analgesic effectiveness. We also believe that bupivacaine injection has no influence on intra- or immediate post-procedural pain.The primary aim of study is to compare the effectiveness of EUS-CPN with and without bupivacaine. Secondary aims include a comparison of intra- and post-procedural pain, narcotic use, adverse events, and survival between the studied groups.This is a single-center, randomized, double-blinded, parallel groups, non-inferiority clinical trial to be performed at the endoscopy unit of the Centre Hospitalier de l’Université de Montréal (CHUM) in Québec, Canada.The SPIRIT reporting guidelines have been used in protocol formulation .All patients referred for EUS for suspected pancreatic malignancy or for neurolysis for pain due to proven pancreatic malignancy are eligible. The study will be presented to them by a single research assistant, who will also obtain study consent before the procedure. Patients will be randomized if they meet all inclusion criteria and have no exclusion criteria presented in Table n = 2 × 7.8 × (7/3) 2 = 2 × 7.8 × 5.4 = 90 per group.The sample size, estimated in relation to the primary outcome, is based on the detection of a minimum clinical difference of 3 points on the Likert scale between the 2 study groups, with a beta error of 20%, an alpha error of 5%, and a standard deviation of 7. Approximately 3000 EUS procedures are performed at CHUM annually, including approximately 300 adenocarcinomas of the pancreatic genu/body/tail, of which 90% (270) are inoperable and have pain. Given a sample size requirement of 90 patients and allowing for a 50% refusal/dropout rate, this study could be completed in approximately one and a half years. This was the approximate time frame for our previous RCT on neurolysis in the same patient population . An extrParticipants will be randomized in 1:1 fashion, by sealed opaque envelopes, prepared by an independent third party, using a list produced by the web-based randomization service Sealed Envelope™.Since the final inclusion criteria (accessibility of the celiac axis by EUS) is determined during the procedure, while the patient is sedated, the patient will be blinded to the treatment arm.The research nurse who collects the data will not be present during the randomization process, nor the procedure, and will therefore also be blinded to the treatment arm.EUS-CPN with bupivacaine: endoscopic ultrasound-guided bilateral celiac plexus neurolysis with absolute alcohol 20 mL preceded by injection of 10 ml of bupivacaine 0.5%EUS-CPN: endoscopic ultrasound guided bilateral celiac plexus neurolysis with absolute alcohol 20 mL onlyPatients will be followed in the immediate post-procedural period until 4 months after the procedure or death whichever comes first; see Fig. Likert pain scores pre-procedure (T0) and 30 min after arriving in recovery (T30) and then every 30 min until dischargeOpioid use in the last 3 days before the procedureVital signs pre-procedure (T0), immediately before and after neurolysis, and at 30 min after arriving in recovery (T30), and then every 30 min until dischargeRequirements for analgesia during the recovery periodImmediate post-procedural surveillance:Post-discharge surveillance:7-point Likert scale for pain Table Global rating scale of change (GRSC) Table Any adverse events Hospital visitsNarcotic use.Telephone interviews by a single research assistant on days 3, 7, 30, 60, 90, and 120* for:*Days 3 and 7: ± 2 days; days 30, 60, 90, and 120: ± 4 daysComparative change in Likert pain scores before procedure (T0) and at 30 days after the procedure Table  with treT0 and all other time points specified above% Difference in 7-point Likert scale and GRSC Table :T0 and aTime to discharge from the endoscopy unitT0 vs T60 daysT0 vs T120 days% Change in cumulative narcotic use for the previous 3-day period:Rate of all intervention-specific adverse events  Survivalt test will be performed when comparing two means. Fisher’s exact method will be used for proportions comparison. All p-values are two-tailed, and values < 0.05 will be considered statistically significant. Subsequent logistic regression modeling will determine the factors that are associated with a better pain outcome.Descriptive statistics will assess patient characteristics  and the balancing of randomization. The data will be tested for normality, and the paired Wilcoxon ranked sum test will assess the pain scores. Student’s Kaplan-Meier estimates of the survival curve will be obtained for each treatment group, and statistical comparisons of these will be performed using the log-rank test. The Cox proportional hazards models will be used to study survival while adjusting for potential confounding factors.Patients who withdraw will be noted and will be noted and they will be excluded from analysis.The CRCHUM Research Ethics Board (REB), more precisely its CT2 Panel, has reviewed this research project at its full board meeting where quorum was reached. It was approved, with number of 2022-9969, 21.151. Approval was communicated to the principal investigator on September 21, 2021. No REB member withdrew from the deliberations. Any protocol modification will be submitted to the REB. We have started recruitment on November 2, 2021, and 36 patients have been recruited to date. The recruitment is expected to continue until the target sample size is reached.This trial was registered at ClinicalTrials.gov with registration number NCT04951804 and conducted at the CHUM only. Charles Mackay RN, who has extensive experience in clinical trials, will ensure proper trial conduct and all data collection. He will ensure proper study start-up and adaptation of the consent form. He will oversee participant enrolment, the randomization process, data collection, the timely reporting of adverse events and serious adverse events to the CRCHUM Research Ethics Board (REB), and data collection. He will ensure adherence to standard operating procedures of the CRCHUM.A selected group of clinicians and clinical researchers will oversee this study’s DSMB. This will include an EUS-MD from outside CHUM. Members of the DSMB will not be involved in the conduct of the trial and their participation will be void of any professional or financial bias that may hinder their independent decision making. This committee will meet before trial initiation and meet every three months to review possible AEs. Each reviewer will be blinded to the group allocation. At the first meeting, the DSMB will discuss the protocol and decide on criteria to review the data as well as monitoring of the study. The following meetings will be divided into an open and close sessions. During the open session, the PI, statistician, and all members of the DSMB will be present. The PI will present to the committee the participants’ demographic characteristics, protocol compliance, quality control, timeliness and completeness of follow-up, and all adverse events. During the closed session, the DSMB alone will review the safety data. At the end of each meeting, the members of the DSMB will vote to continue, modify, or terminate the study. The DSMB will provide a written report to the REB and PIs about their conclusion.Following the signature of informed consent, participants will be given a unique identifier (ID). This study ID will be used in the main database containing study-related data. No identifying information including name, date of birth, or hospital unit number will be in the main database to protect participant confidentiality. A separate password-protected file will contain participants name and study ID information. Only the PI will have access to this file. All data will be stored for 10 years following the study completion or as requested by the standard operating procedure of the CRCHUM.Additional file 1. Copy of the case report form.Additional file 2. SPIRIT checklist.


Spinal cord stimulation (SCS) is a surgical technique used in patients with chronic intractable pain, and its effectiveness and safety have been validated by multiple studies. However, to maintain an optimal and steady long-term effect is still challenging. Here, we report a new management paradigm integrating smartphone application and remote programming. Chronic pain patients with SCS implants can monitor their pain status on the phone and change stimulation parameters accordingly. The PreMaSy study is a randomized controlled trial to evaluate the clinical effectiveness and safety of this precise management system.Patients with chronic intractable pain will be screened for eligibility, and 82 participants are anticipated to be enrolled in this trial. After the electrode implantation, the stimulation effectiveness will be tested. Participants with a reduction of more than 50% in the visual analog scale (VAS) will receive implantation of an implantable pulse generator and randomized (1:1) into the experimental group or control group. All participants will be asked to take online follow-ups and complete assessments using a smartphone application. Daily pain characteristic assessments and monthly quality of life questionnaires are integrated into the App, and participants will be required to complete these assessments. The daily VAS for pain intensity will be monitored and a threshold will be set based on baseline VAS score. The interventional appointment will be scheduled once the threshold is reached. The primary outcome is the health condition and quality of life assessed by the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L). Utility values of EQ-5D-5L will be assessed at baseline and 1, 3, and 6 months post-operative.The PreMaSy study aims to evaluate the effectiveness and safety of a novel App-based, patient-centered, self-assessment management system for chronic intractable pain. A randomized controlled trial is designed to test the non-inferiority of this precise management system compared to the monthly online follow-ups. It is also expected to yield valuable experiences regarding precision medicine.ClinicalTrials.gov NCT05761392. Registered on March 07, 2023.The online version contains supplementary material available at 10.1186/s13063-023-07595-4. As a growing public health concern, chronic pain has an impact on many aspects of patients’ lives. Not only does it affect physical functions and limit daily activities, but it also has a detrimental impact on work, social, and family-related consequences and decreases one’s quality of life . FurtherSpinal cord stimulation (SCS) is a technique that uses implanted electrodes to directly stimulate the dorsal columns of the spinal cord. It has been approved and widely used in a variety of pain control applications, for example, failed back surgery syndrome (FBSS) , complexAttempts are being made to maintain maximum and stable efficacy with minimal financial and time expenditures by utilizing telemedicine and remote programming. Our group has reported for the first time the clinical application of remote programming for pain patients with a SCS implant using a video-based real-time remote programming system . Our remBut we wanted to take one step further. Pain characteristics differ not only across individuals but also within a single individual. For example, the pain intensity may change significantly throughout the day due to weather, mood, or sleep quality, or it may simply vary over time. But these shorter-term shifts are often ignored in both traditional and online programming sessions. Patients have to wait until scheduled follow-up sessions for major adjustments in stimulation parameters. A more precise application-based, patient-centered, self-assessment management scheme has been exploring in a broad range of diseases, for example, Parkinson’s disease , atrial Here, we introduce for the first time a precise management system for pain patients with a SCS implant, which combines self-assessment based on a customized smartphone application (App) and remote programming based on a remote and wireless programming system. In the proposed study, patients who use the precise management system will be compared to those who take conventional online follow-ups. We intend to investigate the effectiveness of this novel system and its application in a broader population.The PreMaSy study is a prospective, double-arm, enrichment-enrollment, randomized-controlled trial  designated to evaluate the effectiveness of the precise management system for chronic intractable pain. The precise management system is a novel App-based, patient-centered, self-assessment modality designed for patients who have chronic intractable pain and are treated with remote and wireless SCS. Compared with a classic RCT, an enrichment-enrollment trial increases the proportion of likely responders in order to maximize the differences between treatment and placebo effects, for example, in many analgetic drug trials , 39. To The timeline of this study is divided into three distinct periods: 1) screen period, 2) test period, and (3) follow-up period  test period. Pain intensity will be monitored during this time. Only participants who have an improvement of no less than 50% in visual analog scale (VAS) will undertake the implantable pulse generator (IPG) implantation. After the IPG implantation, participants will be randomized (1:1) into one of the two groups: the experimental group (EG) with PreMaSy or the control group (CG) with conventional follow-ups. The randomization will be generated by computers and concealed from the recruitment team and data analysis team. The participants and their physicians, however, will not be blinded from their own randomization results, because the consequent assessments are dependent on which group they are in. The detailed assessments of the two groups are shown in Fig. The PreMaSy study protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials Statement (SPIRIT). A SPIRIT checklist is included in Additional file The study will be primarily conducted in the Neurosurgery Center of Beijing Tsinghua Changgung Hospital. Additional centers may be added as the study progresses. The protocol has been approved by the Clinical Trial Ethics Committee of Beijing Tsinghua Changgung Hospital . It is anticipated that the enrollment will end prior to September 2024. And invitations will be sent to our clinic patients experiencing chronic intractable pain during that time.The inclusion criteria are shown in Table The exclusion criteria are shown in Table Our research team in cooperation with Beijing Pinchi Software Development Co., Ltd. developed an App that integrates the wireless control of the stimulation device and the follow-up assessments. The App can connect wirelessly to the IPG device based on our previously developed remote and wireless SCS system . Four seThe assessment module was designed as a crucial element in the precise management system. Four major sections are included: (1) daily assessments, (2) monthly assessments, (3) hardware-related issues, and (4) satisfaction with App usage.x-axis of the curve represents 24 h in a day, while the y-axis represents the VAS score of pain intensity. The participants are asked to recall their pain experience from the previous day and draw a curve to depict the fluctuations in pain intensity over time. As for the spatial features, we referred to the pain area drawing in the Brief Pain Inventory (BPI) and designed a version that is touch-screen compatible. In order to standardize the pain map, the front and rear body projections were separated according to the dermatome pattern. However, the pattern was too detailed to be identified accurately on a smartphone display. Therefore, we consolidated certain consecutive dermatomes and generated 25 gross selection areas  is a widely used instrument for assessing general health that consists of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression . We usedImpedance tests, parameter adjustments, adverse events (AEs), and other hardware-related issues are collected. Participants and their physicians are also asked to take satisfaction surveys based on their App usage experiences and encouraged to provide feedback. All aforementioned assessment modules will be activated automatically when the profile of a participant is established, and in order to enhance compliance, notifications of incomplete assessments will be sent at a set time.During the test period, electrode implantation and IPG implantation will be undertaken in patients who qualify. After surgery, stimulation parameters will be optimized for analgesia. In our prior work, we have described the implantation surgery, stimulation device, and programming procedure in detail . The afoFor participants in CG, they will be scheduled for follow-ups at conventional intervals, i.e., 1, 3, and 6 months post-operative. They can only access monthly assessments during the corresponding months. For participants in EG, on the other hand, the precise management system will be implemented. In addition to the standard follow-ups, they will be asked to complete every monthly assessment throughout the 6-month follow-up period. They will have access to the daily assessments in which they will be instructed to record and track their pain characteristics. Pain intensity VAS data collected after the electrode implantation and prior to the IPG implantation will be averaged and served as the baseline. The interventional threshold will be a minimum clinically significant difference (MCSD) of 20 mm (out of 100 mm VAS)  added toTo improve adherence, the background system will monitor the assessments’ completion status, and specialists will be allocated to inquire about the incompletion. Other concomitant care including medications are only permitted by approval of investigators. Both CG and EG participants have the same access to report hardware-related issues and satisfaction with App usage. In the case of adverse events (AEs) or unexpected worsening, they may also schedule an urgent appointment.As previously stated, EQ-5D-5L is a questionnaire which measures five dimensions. It depicts different health conditions as five-digit numbers corresponding to unique utility values. The primary outcome of the PreMaSy study is the change of EQ-5D-5L utility values between CG and EG at the 6-month follow-up compared to baseline values. After passing the eligibility screening, they will be required to fill up an EQ-5Q-5L questionnaire based on their pain experience prior to enrollment, and this value will serve as the baseline. The primary outcome formula is:The differences in EQ-5D-5L utility values at 1- and 3-month follow-ups compared to baseline will be included in the secondary outcomes. Other secondary outcomes include changes in pain intensity VAS, time-intensity curve, pain map, EQ-VAS score, PSQI, PGIC, CGI-I, and satisfaction with App usage. The occurrence rate of AEs and severe AEs (SAEs) will be used as safety outcomes.The primary comparison in this study is the difference between EG and CG in quality of life score measuring by EQ-5D-5L. The EQ-5D-5L difference is assumed to be 0.53 with a standard deviation (SD) of 0.69 based on previous studies into the effectiveness of App-based therapy for chronic pain . A sampl t test, The primary effectiveness analysis is the 6-month non-inferiority of the within-group difference between CG and EG for the overall health-related quality of life measured by EQ-5D-5L. Non-inferiority will be tested between the two groups at a one-sided significance of 0.05, and if the non-inferiority of the primary endpoint was achieved, superiority will be tested at a one-sided significance of 0.025.t test and ANOVA) will be performed with data of normal distributions. Non-parametric tests  will be performed if parametric tests are not indicated. All statistical analyses will be performed in a validated statistical software package .For secondary endpoints, non-inferiority will be also tested with a 10% non-inferiority margin and a one-sided significance of 0.05. Secondary endpoints include changes from baseline of EQ-5D-5L scores in 1 and 3 months, VAS scores, time-intensity curves, pain map, EQ-VAS scores, PSQI, PGIC, CGI-I, and satisfaction with App usage. Continuous variables will be summarized using means and standard error, and categorical variables will be summarized using frequency distributions. Parametric tests  will monitor, audit, and assure compliance with the protocol, GCP, and regulatory requirements during data collection.SCS is one of the surgical approaches for patients with chronic intractable pain. It is sometimes seen as “the last resort therapy” for those who do not respond well to medications or other non-surgical treatments. Since the first implanted SCS system in 1967 , signifiConventional frequency SCS (CF-SCS) delivers a frequency of 10 to 300 Hz. It targets the spinal inhibitory GABA system and usually generates parenthesias . High-frThere are still challenges in the SCS field. The first one is to optimize the efficacy, which requires the personalization of stimulation paradigms according to each patient’s need. But the efficacy can be affected by multiple variables, including but not limited to stimulation parameters, lead location, patient anatomy, and pain pattern . PersonaTo address these challenges, efforts were made in the developments of neurostimulation technologies . AdvanceEfforts on developing such Apps have already been made in the management of chronic pain , 28. HowIn our customized App, information on patient education and assessments of semiological monitoring are provided as basic functions, which is consistent with other Apps , 28. ForThere are some limitations in this study. The primary objective is to determine whether this new precise management system is noninferior to conventional online follow-ups. However, the evidence of App effectiveness is still absent. The effect due to the different intensities of App usage cannot be fully interpreted. Another limitation is that the intervention cannot be blinded because it makes direct changes in patients’ lifestyle and relies on their feedbacks. In addition, the overall duration of follow-ups is only 6 months, which is insufficient for exploring long-term consequences and reducing placebo effects.Protocol version 1.3 . The recruitment began in September 2022 and is expected to be completed in September 2024.Additional file 1. Reporting checklist for protocol of a clinical trial.


Postoperative pain control can be challenging in patients undergoing hepatectomy. A previous retrospective study on hepatobiliary/ pancreatic surgeries showed better postoperative pain control in patients who received propofol TIVA. The aim of this study was to determine the analgesic effect of propofol TIVA for hepatectomy. This clinical study has been registered at ClinicalTrials.gov (NCT03597997).A prospective randomized controlled trial was performed to compare the analgesic effect of propofol TIVA versus inhalational anaesthesia. Patients aged between 18 and 80 years old with an American Society of Anesthesiologist (ASA) physical status of I-III scheduled for elective hepatectomy were recruited. Ninety patients were randomly allocated to receive either propofol TIVA (TIVA group) or inhalational anaesthesia with sevoflurane (SEVO group). Perioperative anaesthetic/analgesic management was the same for both groups. Numerical rating scale (NRS) pain scores, postoperative morphine consumption, quality of recovery, patient satisfaction and adverse effects were evaluated during the acute postoperative period and at 3 and 6 months after surgery.p = 0.014, and FDR < 0.1). TIVA group was associated with better quality of recovery on postoperative day (POD) 3 , less nausea  and constipation .No significant differences were found for acute postoperative pain scores (both at rest and during coughing) and postoperative morphine consumption between TIVA and SEVO groups. Patients given TIVA had lower pain scores with coughing at 3 months after surgery (Propofol TIVA did not improve acute postoperative pain control compared to inhalational anaesthesia in patients who underwent hepatectomy. Our results do not support the use of propofol TIVA for reducing acute postoperative pain after hepatectomy. It can be used in total intravenous anaesthesia (TIVA) to maintain general anaesthesia throughout surgery without using inhalational anaesthetics . Some ofogeneity .The postoperative analgesic effect of propofol TIVA is perhaps influenced by the types of surgery and accompanying analgesic regimes . Liver rA prospective randomized controlled trial is the reasonable next step to determine propofol TIVA’s analgesic effect for hepatectomy. The main objective of this study is to investigate the effect of propofol TIVA on acute pain intensity and opioid consumption after hepatectomy when compared to inhalational anaesthesia. We hypothesize that propofol TIVA would reduce postoperative pain scores and opioid consumption.This study was conducted at Queen Mary Hospital in Hong Kong, China. The study was approved by the Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 18–176), and registered at clinicaltrial.gov prior to patient recruitment on 24/07/2018 (NCT03597997). All methods were carried out in accordance with relevant guidelines and regulations. Written informed consent was obtained from all patients participating in the trial.2; 6) history of chronic pain; 7) pregnancy; 8) local infection; 9) history of psychosis; 10) delirium; 11) chronic opioid user; or 12) patient refusal [This study was prospective, double-blinded randomized controlled, conducted in accordance to the CONSORT guideline. All methods were carried out in accordance with Declaration of Helsinki. Patients aged between 18 and 80 years old with an American Society of Anesthesiologist (ASA) physical status of I-III scheduled for elective hepatectomy  were eligible. Exclusion criteria included the following: 1) known drug allergy to propofol, opioids, and non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors, paracetamol, ketamine; 2) alcohol or drug abuse; 3) impaired renal function, defined as preoperative serum creatinine level over 120 µmol/L; 4) impaired or retarded mental state; 5) body mass index (BMI) > 35 kg/m refusal .Eligible patients were approached in the general ward before the operation for recruitment. The anaesthetic options were explained, and the patient was recruited into the study if s/he agreed. The patients were then randomized into one of two groups: i) SEVO group, anaesthetized by inhalational anaesthesia using sevoflurane; or ii) TIVA group, anaesthetized using propofol total intravenous anaesthesia. Patients recruited for hepatectomy were stratified in randomization. A computer-generated random sequence was used to select the allocation order, which was concealed in opaque envelopes, and opened at the time of intervention administration. Patients were not aware of the types of anaesthesia they received. A separate blinded investigator assessed the patients after the operation. The anaesthetist providing general anaesthesia was aware of the allocation, but s/he was not involved in data collection. Assessment was done at the general ward. Fasting for patients started at midnight before operation . Premedi2 was be kept between 35–50%. Bispectral Index (BIS) monitoring was applied and the level of anaesthesia was titrated to maintain a BIS value of between 40–60. Intravenous remifentanil infusion between 0.1–0.2 mcg/kg/min was given during surgery and titrated to provide optimal haemodynamic parameters. Ondansetron 4 mg IV was given 30 min before the end of surgery. Sevoflurane and remifentanil infusion were switched off at the end of the procedure. Reversal of muscle relaxation was obtained with neostigmine 50mcg/kg IV and atropine 20mcg/kg IV after the operation. Patients were transferred to the post-anaesthetic care unit (PACU) for monitoring for at least 30 min. The anaesthetic and analgesic protocol for patients in the TIVA group was the same as the SEVO group. The only difference was that the induction and maintenance of general anaesthesia was performed using propofol total intravenous anaesthesia. Sevoflurane was not used, and oxygen and air were given. Target controlled infusion (TCI) with modified Marsh effect site model (Fresenius Kabi) was used for induction and maintenance of general anaesthesia. Level of anaesthesia was titrated to produce a BIS value of between 40–60. During induction of general anaesthesia, remifentanil 0.5-1mcg/kg, and rocuronium 0.6-1 mg/kg or atracurium 0.5 mg/kg were given IV. Remifentanil infusion was given as per SEVO group [On arrival to the operation theatre, a 20- or 22-gauge intravenous cannula was inserted. Standard monitoring with pulse oximeter, non-invasive blood pressure, and three lead electrocardiograms was applied prior to induction. For patients in the SEVO group, general anaesthesia was induced with propofol 1.5-3 mg/kg, remifentanil 0.5-1mcg/kg, and rocuronium 0.6-1 mg/kg or atracurium 0.5 mg/kg given intravenously (IV). Sevoflurane, air and oxygen was used for maintenance of general anaesthesia. FiOVO group .For both groups of patients, morphine sulphate at a bolus dose of 0.1 mg/kg IV was given before skin incision. Additional 0.1 mg/kg of morphine sulphate IV could be given in divided doses when the surgery continued for more than 2 h at the discretion of the attending anaesthetist. Ketamine 0.5-1 mg/kg IV was given before skin incision. Patients received local wound infiltration with up to 2 mg/kg of levobupivacaine during wound closure . This waResting pain scores were checked every 5 min in the PACU. Morphine sulphate at a dose of 2 mg IV was given every 5 min until the numerical rating scale (NRS) pain score was less than 4/10. Respiratory rate, oxygen saturation, Ramsay sedation scores, blood pressure and heart rate were monitored every 5 min in the PACU. Patient controlled analgesia (PCA) morphine was connected to the patient once the NRS pain score was less than 4/10. The following parameters were set for the PCA morphine machine: bolus 1 mg of intravenous morphine sulphate with each patient demand, lockout duration of 5 min, and maximum dose limit of 0.1 mg/kg of morphine sulphate per hour. When the patient resumed fluid diet in the ward on POD 0, regular oral dihydrocodeine was prescribed at a dose of 30 mg three times a day for two days. Afterwards, dihydrocodeine was given as needed. Breakthrough pain was treated by intramuscular/subcutaneous morphine 0.1 mg/kg every 4 h as needed starting from POD 0 . Pain rePCA morphine was given for at least 2 days. It was stopped on POD 2 if NRS pain scores during coughing were less than 4/10 and morphine consumption was low. PCA morphine was continued if NRS pain scores during coughing were equal or greater than 4. After discontinuation of PCA morphine, NRS pain scores (at rest and during coughing) and the dose and frequency of rescue analgesia used were recorded daily until patient discharge. Patient satisfaction with analgesia, where 0 corresponded to the least satisfaction, and 10 corresponded to the most satisfaction, was assessed on POD 1 . QualityVarious outcomes were also assessed at 3 and 6 months after surgery. This included the presence or absence of pain, and NRS pain scores at rest and with coughing . PatientThe primary outcome was the NRS pain score during coughing on POD 1. Our previous retrospective study on hepatobiliary and pancreatic surgery had shown that the mean (SD) of NRS pain score during coughing on POD 1 for TIVA group was 4.30 (1.99) . To detep-value < 0.05 with an FDR value < 0.1 was regarded as statistically significant [For patient demographics and intraoperative analgesic consumption, continuous data were analysed using independent-samples t-test or Mann–Whitney U test, and categorical data were analysed using Pearson Chi-square test or Fisher’s Exact test. HRQOL domains for SF-12, satisfaction with analgesia and psychological condition were compared with Mann–Whitney U test. The standardized pain scores both at rest and during coughing were expressed as area under curve (AUC) weighted by the corresponding time interval. The weighted AUC was equivalent to a time weighted average of the pain scores for the specified time interval, and was of the same scale as the NRS (0–10). The difference in the standardized pain scores between the TIVA and SEVO groups were compared using the Mann–Whitney U test, and expressed as median (interquartile range). The cumulative PCA morphine consumption at 24, 48 and 72 h after the surgery between the two groups was also compared using the Mann–Whitney U test. Incidence of adverse effects was compared using the Chi-square test or Fisher’s exact test as appropriate. IBM SPSS Statistics Version 27.0 (IBM Corp. USA) was used to analyse the above data. False discovery rate (FDR) is the expected proportion of the rejected null hypotheses that are actually true, and it is a recommended alternative in health-related studies , 23. Benn = 56) or inhalational sevoflurane (n = 54). Six patients in the TIVA group and five patients in the SEVO group were excluded. A total of 99 recruited patients completed the study for primary outcome measure. Five patients in the TIVA group and four patients in the SEVO group were excluded due to insufficient data, and the results of the remaining 90 patients were used for analysis. At 3 and 6 months after surgery, 16 patients in the TIVA group and 8 patients in the SEVO group were lost to follow up, leaving 29 patients in the TIVA group ad 37 patients in the SEVO group for analysis  completed the study, which was conducted from August 2018 to July 2021. One hundred and eighteen patients were assessed for eligibility, and eight were excluded. Six patients declined to participate and two patients did not join due to medical decisions. A total of 110 patients were randomly assigned to undergo anaesthesia, either with propofol TIVA   and POD 3 , and constipation  on POD 2. There was a statistically significant increase in overall adverse effects on POD 2 in the SEVO group compared to the TIVA group   and during coughing  (Table 1) Table . There w1) Table . No signp = 0.014, and FDR < 0.1), but there was no difference at rest  on POD 3. The analgesic effect of propofol TIVA for acute postoperative pain control is not certain. A previous meta-analysis showed a small reduction in postoperative pain intensity and opioid consumption with propofol TIVA . Anotherogeneity . The anaPostoperative pain control after hepatic surgery can be challenging to manage. Hepatic surgery is associated with upper abdominal wounds, which results in more severe postoperative pain when compared to lower abdominal wounds, especially with coughing . PatientPatients in the TIVA group had reduced nausea and constipation, and better quality of recovery on POD 3. The quality of recovery (QoR) score is a measure of the health-related quality of life after surgery and anaesthesia . A good In a previous retrospective case–control study, propofol TIVA was associated with lower acute postoperative pain scores and postoperative opioid consumption after hepatobiliary and pancreatic surgeries . HoweverThere were some limitations in this randomized controlled trial. The first limitation was a relatively small sample size. The sample size was calculated based on our previous retrospective study on hepatobiliary and pancreatic surgery, which was not only restricted to hepatectomy . A largeIn conclusion, propofol TIVA did not improve postoperative pain scores or reduce opioid consumption after hepatectomy when compared to inhalational anaesthesia. Propofol TIVA was associated with better QoR on POD 3 and lower pain scores with coughing at 3 months after surgery. It was also associated with a lower incidence of nausea and constipation, which is not likely related to propofol’s analgesic effect. Our results do not support the use of propofol TIVA for the purpose of reducing acute postoperative pain after hepatectomy when used together with ketamine. However, other outcomes such as effects on adverse events and quality of recovery should be considered when choosing between general anaesthetic techniques.


The Shoulder and Pain Disability Index (SPADI) is a widely used outcome measure. The aim of this study is to explore the reliability and validity of SPADI in a sample of patients with idiopathic frozen shoulder.The SPADI was administered to 124 patients with idiopathic frozen shoulder. A sub-group of 29 patients were retested after 7 days. SPADI scores were correlated with other outcome measures  to examine construct validity. Structural validity was assessed by a Two-Factors Confirmatory Factor Analysis (CFA). Internal consistency, test–retest reliability, and measurement error were also analyzed.The construct validity was satisfactory as seven out of eight of the expected correlations formulated (≥ 75%) for the subscales were satisfied. The CFA showed good values of all indicators for both Pain and Disability subscales . Internal consistency was good for pain (α = 0.859) and disability (α = 0.895) subscales. High test–retest reliability (Intraclass correlation coefficient [ICC]) was found for pain  and disability (ICC = 0.990 [95% CI = 0.988–0.998]). Standard Error of Measurement values of 2.27 and 2.32 and Minimal Detectable Change values of 6.27 and 6.25 were calculated for pain and disability subscales, respectively.The SPADI demonstrated satisfactory reliability and validity properties in a sample of patients with idiopathic frozen shoulder. Idiopathic Frozen Shoulder (FS) is often characterized by severe shoulder pain and functional restrictions of both active and passive shoulder motion . These rDelays in the clinical diagnostic process incomplete or unclear prognostic information, and lack of a standard rehabilitation program are issues that may increase the patients’ frustration and the socio-cultural impact that FS has on their life . FS geneIn order to achieve an effective therapeutic alliance, it is essential to use clear and valid information that is based on the best available evidence. This will allow a tailored rehabilitation program to be developed based on the patient's needs and fears. In this context, health indicators could be used to overcome the discrepancy between clinicians’ and patients' perceptions  of disabBased on our literature review, only one study has assessed the responsiveness of the Shoulder Pain and Disability Index (SPADI) in a sample of patients with FS, which demonstrated that it could be an appropriate PROMs to assess the point of view of this population . This sea) gradual and progressive onset of shoulder pain; b) a restriction of both glenohumeral active and passive ROM in multiple planes; c) sleep-disturbing night pain and/ or firm end-feel at the end ranges of movements, especially in external rotation at variable degrees of shoulder abduction that occurs for at least 1 month [Patients were recruited through convenience sampling in two Italian private physical therapy clinics, over a 3-year period between 2019 and 2021 if they met the following inclusion criteria: 1) over 18 years of age; 2) clinical diagnosis of idiopathic FS by orthopedic surgeons and physiotherapists based on the following findings:  1 month . Patient 1 month , secondaAll procedures involving human participants were in accordance with the Helsinki declaration and its later amendments. Personal information and informed consent were obtained from all patients to participate in this study.The Italian version of the SPADI used in this study was cross-culturally adapted and validated by Marchese C, et al., available elsewhere . The SPABefore the compilation process, patients were instructed to place a mark on the Visual Analogue Scale (VAS) for each of the 13 items . The resThe DASH is an outcome measure that assesses the ability of an upper extremity to perform activities of daily living regardless of the site(s) and nature of musculoskeletal pathology . The DASThe NPRS is an eleven-point measure of pain: the patient rates pain from 0 (no pain) to 10 (worst imaginable pain) . The NPRThe SF-36 is a tool that assesses Health-Related Quality of Life . The SF-The SPADI was administered to each patient together with the DASH, NPRS, and SF-36. Clinical and demographic data were also acquired during the recruitment phase  through an interview conducted by a physiotherapist. Each questionnaire was self-reported by the patients.This study has followed the definitions and procedures proposed by the COSMIN initiative  in the pStructural validity was assessed by a two-factors Confirmatory Factor Analysis (CFA)  using thReliability was assessed as internal consistency, test–retest reliability, and measurement error. These analyses were performed on both subscales (Pain and Disability) separately. Internal consistency was evaluated according to these criteria: 1) Cronbach’s Alpha (α) , where v2,1) with 95% Confidence Intervals (CI) [To examine test–retest reliability, the Intraclass Correlation Coefficient   was calcals (CI) , but valals (CI) . The Staals (CI) . The SEMThe outcome measures were used for a comparative analysis to study the validity of two constructs: for pain, the SPADI Pain subscale score was correlated with the NPRS; for disability, the SPADI Disability subscale score was correlated with the DASH score even though the DASH measures disability of the upper limb and is not specific to the shoulder .a-priori hypothesis test using the magnitudes of the Spearman’s rank correlation (rs) coefficients between the SPADI and the other three scales .The cut-offs of rs > 0.60, 0.30 < rs < 0.60, and rs < 0.30 represent strong, moderate, and weak correlations, respectively [Construct validity was examined through an ectively . Construectively .a-priori hypotheses testing was conducted for the following assumptions:Based on the expected correlations, an the positive correlation between the Pain subscale and the NPRS scores is > 0.60 because they measure the same construct, and this correlation value was found in another SPADI validation study ;the positive correlation between the Pain subscale and the DASH total scores is > 0.60 as found in other SPADI validation studies , 49;the negative correlation between the Pain subscale and the Physical Functioning (PF) subscale of the SF-36 is > 0.30 since shoulder pain globally compromises the physical health status ;the negative correlation between the Pain subscale and the Bodily Pain (BP) subscale of the SF-36 scores is > 0.30 and < 0.60, based on their similar constructs.- For the Pain subscale:the positive correlation between the Disability subscale and the DASH total scores is > 0.60, as reported in other SPADI validation studies , 48, 49;the positive correlation between the Disability subscale and the NPRS scores is between > 0.30 and < 0.60, since pain showed a moderate correlation with disability in similar patients , 47;the negative correlation between the Disability subscale and the Role Physical (RP) subscale of the SF-36 scores is > 0.30 , 51;the negative correlation between the Disability subscale and the Social Functioning (SF) subscale of the SF-36 scores is > 0.30 , 51.- For the Disability subscale:p < 0.05 for all analyses.The R-package lavaan was used to run the CFA, while the SPSS package, version 21 for Windows  was used for all other statistical analyses. Statistical significance was set as One hundred and twenty-four  subjects with FS were included in this study. Detailed demographic and clinical characteristics are presented in Table Considering the results of the CFA applied on the two SPADI subscales (Pain and Disability), good values were found for all indicators. The CFA results revealed a two-factor structure .Internal consistency findings are reported in Table 2,1 (95% CI) of 0.989 (0.975–0.995) for the Pain subscale and 0.990 (0.988–0.998) for the Disability subscale.The results on reliability are shown in Table a-priori hypotheses between SPADI subscales and the other scales administered to patients are reported in Table The correlation coefficients of the a-priori hypotheses were satisfied.The construct validity for each subscale was satisfactory. Four out of four (100%) for the Pain subscale and three out of four for the Disability subscale (75%) of the The present study suggests that SPADI can be used to assess pain and disability in patients with FS , given tConfirmatory factor analysis in our data revealed that SPADI has two dimensions . The CFA showed well-fitting values with a CFI of 0.999, a TLI of 0.997, and a low error value with an RMSEA of 0.030 and an SRMR of 0.051. The two-dimensions of the SPADI are consistent with findings from the original version of the questionnaire , the Spaα = 0.859) and Disability (α = 0.895) subscales. These values are consistent with those found in other studies including the development of the SPADI (in English) [The internal consistency of the SPADI was satisfactory in the Pain (English) , a ChineEnglish) , in a SpEnglish) , and in English)  or surgeEnglish) .; α = 0.902): this action fully involves shoulder abduction and external rotation and is one of the most provocative action in a patient with FS [The strong agreement between the internal consistency values for Pain and Disability subscales found in this study and those of the original version demonstrates the effectiveness of this questionnaire in assessing FS. Despite the internal consistency of each subscale, the α if-item-is-deleted of item #9 from the Disability subscale indicates a discordant value and reveals the redundancy of the item in relation to the consistency of the entire questionnaire . This re with FS .s values. Weaker relationships between SPADI and SF-36 was also observed in another Italian validation study [The construct validity of each subscale was remarkable, with 4/4 (100%) hypotheses satisfied for the Pain subscale and 3/4 (75%) hypotheses satisfied for the Disability subscale. The analysis of the construct validity brings to light knowledge similar to those that can be found in the literature , 49, 51;on study  and coulon study . Howeveron study –62. ConsThe standard deviation for the pain duration presented in Table n = 76) and only reported test–retest reliability and responsiveness of the SPADI.According to COSMIN, a necessary condition for the use of the total score in clinical practice is that the total score is unidimensional , 46. MorIt is worth noting the following limitations of this study: the results may lack generalizability, as this study only included patients with Idiopathic FS. Therefore, the results of this study should be applied in clinical practice only to patients diagnosed with FS. Moreover, the test–retest reliability sample consisted of only 29 patients; hence, these findings should be taken with caution. Further studies should be designed to assess other psychometric properties such as responsiveness and content validity. Finally, modern psychometric analyses  were not used to further investigate psychometric properties such as structural validity.In conclusion, SPADI has good internal consistency, reliability, and validity in a sample of patients with FS. Future studies should confirm responsiveness, interpretability, and content validity, as these properties have not been studied.


Knee osteoarthritis (KOA) primarily presents with symptoms of pain and compromised functionality. Pain is a subjective manifestation that necessitates the employment of reliable evaluation tools for practical assessment, thereby enabling the formulation of appropriate interventional strategies. The Brief Pain Inventory (BPI) is a widely utilized questionnaire for evaluating the status of chronic pain. The purpose of the present study is to translate the short form of BPI into Chinese version (BPI-CV) and conduct cross-cultural adaptation to evaluate the psychometric characteristics of BPI-CV in KOA patients.α value (> 0.7). We chose to employ two scales commonly used in the evaluation of KOA patients: the disease-specific WOMAC scale and the universal EQ-5D scale. Construct validity was determined through Pearson correlation analysis, comparing BPI scores with those obtained from the WOMAC and EQ-5D scales. Exploratory factor analysis was used to structural validity.BPI-CV was translated and cross-culturally adapted according to internationally recognized guidelines. A cohort comprising 150 patients diagnosed with KOA successfully completed the demographic questionnaire, BPI-CV, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the EuroQoL Group's five-dimension questionnaire (EQ-5D). Internal consistency and test–retest analysis were used to evaluate the reliability. The internal consistency of the scale items was evaluated by calculating the Cronbach's α for assessing internal consistency was 0.894. Test–retest reliability was excellent with an ICC of 0.852 (95%CI 0.785–0.905). The BPI-CV showed moderate to strong correlations with the pain dimension (r = 0.496–0.860) and the functional interference dimension (r = 0.517–0.712) of the WOMAC and the EQ-5D (r = 0.527–0.743). Three factors resulted using exploratory factor analysis: pain severity, activity interference, and emotional interference, accounting for 79.0% of the total variance. Standard error of measurement was 0.539.The BPI-CV was well accepted with no ceiling or floor effect. Cronbach's BPI-CV has good feasibility, reliability, and validity. It can be recommended for KOA patients in mainland China.The online version contains supplementary material available at 10.1186/s13018-023-04218-1. Knee osteoarthritis (KOA) is one of the most common chronic diseases , 2. PainThe Brief Pain Inventory (BPI) is an validated, reliable, and commonly used instrument that can assess the location and severity of pain and its impact on pain individuals . BPI wasCurrently, English and Norwegian studies have reported that BPI has favorable psychometric properties in osteoarthritis patients , 14. As The five steps of translation and cross-cultural adaptation follow the previous guidelines . In the According to the rule of 10 patients for each scale item, at least 110 participants are required to fully evaluate the reliability parameters . From JaThe inclusion criteria of the present study are as follows: (a) age > 18 years old; (b) the cognitive level can meet the requirements of filling in the questionnaire; and (c) fluent Mandarin at conversational level. Exclusion criteria are as follows: (a) history of other vascular, neural, and musculoskeletal diseases that affect activities or produce pain symptoms and (b) serious diseases that affect daily life, such as heart disease, dyspnea, psychosis, etc. All involved participants signed the informed consent form, and the medical ethics committee of Honghui Hospital approved this prospective observational study (No. 202212003).Each participant must complete a general demographic information questionnaire, including age, gender, height and weight ), education level, employment status, living conditions, and pain duration, and then complete three questionnaires, including BPI-CV, WOMAC, and EQ-5D. All questionnaires are managed by well-trained interviewers.BPI is a short, self-management questionnaire. BPI has two main scores: pain severity score and pain interference score. The pain severity score is calculated according to four items of pain intensity, which are, respectively, the "most severe," "at least," and "average" pain of the patient in the past 24 h and the "current pain" (the pain when completing the questionnaire). The score of each item ranges from 0 = "no pain" to 10 = "the most severe pain you can imagine" and contributes to the final score with the same weight, ranging from 0 to 40. The pain interference score is calculated according to the seven subitems of the pain interference item, which include assessing the interference degree of their pain on "life enjoyment," "general activities," "walking ability," "emotion," "sleep," "normal work," and "relationship with other people." The seven subitems are rated from 0 = "no interference" to 10 = "complete interference," ranging from 0 to 70 .The WOMAC stands as a validated and reliable measure extensively employed for evaluating individuals afflicted by osteoarthritis . Its widEQ-5D is a multi-dimensional health-related quality of life (HRQoL) measurement scale . The EQ-Kolmogorov–Smirnov test is used to test the normality of the total scores of BPI, WOMAC, and EQ-5D. Continuous variables were presented with mean values (SD), and categorical variables were presented with numbers (percentages). Statistical analyses were performed using SPSS 24.0 . The significance level was set to 0.05.Record any difficulties encountered by each participant in answering. Record the time required to complete the questionnaire.The floor and ceiling effect is calculated by calculating the proportion of participants with the lowest or highest score of the BPI. If more than 15% of the participants reach the highest or lowest score, this indicates that the corresponding dimension has ceiling or floor effect .Reliability contains internal consistency and test–retest reliability. Internal consistency refers to the degree of correlation between items. It is measured by Cronbach's alpha, which should be greater than 0.7 under ideal conditions . The tesStandard error of measurement (SEM) is an indicator of absolute reliability, reflecting the systematic and random error of the instrument . SEM wasThe simplified Chinese version of WOMAC and EQ-5D has been widely used in mainland China, and its validity and reliability were rigorously tested , 25. TheBecause the factor structure of the BPI varies in different diseases, structure validity was investigated with an exploratory approach using an exploratory factor analysis (EFA) to assess the number of factors. The adequacy was calculated by the Kaiser–Meyer–Olkin test and Bartlett's sphericity test. Principal component analysis was normalized using the Kaiser maximum variance rotation method. The cutoff for load was set to 0.6.Detailed demographic and clinical characteristics of participants are shown in Table There were no missing data in any individual item of the BPI-CV or any of the other two scales. The time required to complete the BPI-CV was 4.9 min (SD 0.5).Floor and ceiling effects for BPI-CV are shown in Table The Cronbach α of BPI-CV is shown in Table r = 0.769), while moderate correlations were found with the EQ-5D (r = 0.527). The function interference dimension had strong correlations with both the WOMAC (r = 0.684) and the EQ-5D (r = 0.743). The emotional interference dimension had moderate correlations with the WOMAC (r = 0.512), while strong correlations were found with the EQ-5D (r = 0.650). The EQ-5D reveals a strong correlation of 0.768 with the BPI-CV, indicating a significant relationship between health-related quality of life and pain assessments.The correlations of BPI-CV with WOMAC and EQ-5D are shown in Table P < 0.001). After exploratory factor analysis, it was loaded on three factors, namely, pain intensity, activity interference, and emotional interference. Table The Kaiser–Meyer–Olkin (KMO) measure of sampling adequacy value was 0.852 with a statistically significant Barlett sphericity  [r = 0.87–0.91) [Internal consistency for all versions of the BPI was expressed using the Cronbach α coefficient. The Cronbach α coefficient for the BPI-CV in the present study was 0.894, which is generally consistent with the English version (0.86–0.96) , the Nor77–0.88) , 30 and 87–0.91) .r = 0.496–0.860) and the functional interference dimension (r = 0.517–0.712) of the WOMAC and weakly correlated with the WOMAC stiffness dimension (r = 0.152–0.367), probably because the BPI mainly assesses pain and functional interference and does not assess stiffness with specific items. This observation result is basically consistent with the trend of the results observed in the Norwegian version [r = 0.768). All these results indicate that BPI-CV has qualified construct validity.In terms of construct validity, the results of the present study showed that the BPI-CV was moderately to highly correlated with the pain dimension r = 0.96–0.860 The structural validity of the BPI-CV was verified using exploratory factor analysis. The results of the Turkish version , 30 and Since BPI was originally developed to assess the pain severity and impact of cancer patients and evaluate the analgesic effectiveness for these patients, we have adapted the original BPI to better evaluate the pain status of KOA patients. First, the first item of the original BPI is to ensure that the scale is only used for cancer pain patients, while the present study is mainly used for KOA patients, so we decided to delete this item . SecondlMoreover, it is important to acknowledge that our research has certain limitations. Firstly, the lack of longitudinal data poses a challenge in accurately measuring responsiveness, such as determining the smallest clinically significant difference or impact size. Secondly, the patient sample primarily consists of individuals from central and western regions of China, which may not be fully representative of the entire Chinese population. To address these limitations, we aim to conduct a multi-center study in the future investigations.In conclusion, we have successfully translated and adapted the BPI-CV instrument. The translated and adapted version has demonstrated good feasibility, reliability, and validity. The BPI-CV serves as a simple, valid, and reliable tool for assessing subjective experiences of pain severity, activity interference, and emotional interference in patients with KOA.Additional file 1. Chinese version of the Brief Pain Inventory.


Background: Intercostal neuralgia is pain associated with the intercostal nerves along the rib, chest, and upper abdominal wall. Intercostal neuralgia has various etiologies, and current conventional treatment options include intercostal nerve blocks, nonsteroidal anti-inflammatory drugs, transcutaneous electrical nerve stimulation, topical medications, opioids, tricyclic antidepressants, and anticonvulsants. For a subset of patients, these conventional treatment options provide little relief. Radiofrequency ablation (RFA) is an emerging procedure for the treatment of chronic pain and neuralgias. Cooled RFA (CRFA) is a specific type of RFA that has been trialed as a treatment for intercostal neuralgia in patients refractory to conventional treatment modalities. This case series assesses the efficacy of CRFA for the treatment of intercostal neuralgia in 6 patients.Case Series: Three female and 3 male patients underwent CRFA of the intercostal nerves to treat intercostal neuralgia. The patients had an average age of 50.7 years and demonstrated an average pain reduction of 81.3%.Conclusion: This case series suggests that CRFA may be an effective treatment option for patients with intercostal neuralgia that is not responsive to conservative treatment options. To determine the duration of pain improvement, large research studies need to be conducted. Intercostal nerves arise from the anterior rami of the thoracic spinal nerves.4 Each nerve enters the appropriate intercostal space between the posterior intercostal membrane and the parietal pleura.4 After entering the intercostal space, the nerve advances to the subcostal groove of the rib.4 Causes of intercostal neuralgia include postoperative complications, traumatic injuries, neoplasms or postirradiation tumors, inflammation, chest tube placement, mastectomy, and infection of an intercostal nerve.9 Most commonly, intercostal neuralgia arises from a previous operation or from infection of an intercostal nerve.1Intercostal neuralgia is any painful condition of the intercostal nerves along the rib, chest, and upper abdominal wall3 While the proportion of individuals suffering from abdominal pain is not known, females are up to 4 times more likely than males to suffer from chronic abdominal wall pain.3 Intercostal neuralgia is an umbrella term, so its specific prevalence cannot easily be determined.1Generalized thoracic pain is prevalent in about 15% of the population, and approximately 40% of patients experience postthoracotomy pain.10 topical medications; opioids; anti-depressants;11 anticonvulsants;13 transcutaneous electrical nerve stimulation; and thoracic, epidural, and intercostal nerve blockade.5 However, these treatments have variable consequences and many patients do not experience significant, lasting reductions in their pain. Side effects associated with selective serotonin reuptake inhibitors are generally mild but include weight gain and sexual dysfunction.11 Side effects associated with tricyclic antidepressants include anticholinergic effects, orthostatic hypotension, and cardiovascular effects.11 Nausea, vomiting, constipation, physical dependance, tolerance, dizziness, sedation, and respiratory depression are all common side effects of opioids.14 Rapid absorption of local anesthetic with intercostal nerve blockades can lead to high systemic blood levels.6Conventional pain management modalities used with intercostal neuralgia include nonsteroidal anti-inflammatory drugs (NSAIDs);15 In this minimally invasive procedure, radio waves with a frequency of 100,000 to 500,000 Hz are applied near a target nerve with the intent to alter the nociceptive pathways of the nerve and thereby lessen the patient's pain.17 Cooled RFA (CRFA) is similar to conventional RFA, but in CRFA, water circulated inside the interior of the single-needle electrode tip18 intermittently cools the electrode tip. The goal tissue temperature of both RFA and CRFA is 80 °C; however, the device temperature is set to 60 °C for the CRFA procedure and 80 °C for the conventional RFA procedure. The lower temperature in CRFA helps prevent blood coagulation and tissue charring, keeping the pathway of the electrode clear for larger ablations than obtained with conventional RFA.19 When needed, multiple electrodes can be used during CRFA for larger treatment areas.18 Compared to the lesions produced with commercially available noncooled electrode tips, CRFA generates larger lesions.20The discovery and development of alternate treatments for intercostal neuralgia are essential to improve patient outcomes. Radiofrequency ablation (RFA) uses radiofrequency energy to create heat to achieve tissue necrosis.2 Because CRFA generates a larger lesion than conventional RFA, we hypothesized that CRFA may be an efficacious treatment option for patients with intercostal neuralgia. This case series describes the efficacy of CRFA treatment for 6 patients with intercostal neuralgia refractory to conventional treatment measures. This case series underwent institutional review board review and received an exemption.RFA has been demonstrated to successfully treat resistant intercostal neuralgia.After informed consent and preprocedure vitals were obtained, patients were placed in the prone position. The thoracic area of the target intercostal nerves was prepped with chlorhexidine and draped in sterile fashion. Lidocaine 1% was injected as local skin wheal anesthesia. Under fluoroscopic guidance, a 17-gauge, 50-mm needle with a 4-mm active tip was inserted and advanced until the needle was in contact with the inferior border of the target rib. The needle was then walked off the rib to just underneath the inferior edge. The same needle insertion was replicated for all target intercostal nerve spaces. RFA probes were inserted into each needle, and motor testing was performed for confirmation of placement. Each RFA probe was injected with 1 mL of lidocaine 2%. In lesion mode, CRFA was performed for 165 seconds to the tissue with a machine setpoint of 60 °C and a target tissue temperature of 80 °C around the electrode tip. After the procedure duration, the needles were removed, the skin was cleaned, and sterile dressing was applied.All of the patients who underwent CRFA of the intercostal nerves met our defined criteria for intercostal neuralgia refractory to conservative management. Patients were eligible for intervention if they experienced chronic rib, chest, or upper abdominal wall pain attributable to intercostal neuralgia and did not experience adequate relief following conservative management with a combination of pharmacotherapy, physical therapy, heat, ice, and rest. All 6 patients received preprocedural diagnostic intercostal nerve blocks. None of the patients reported any increase in pain during the procedure, and all 6 patients tolerated the procedure well.A 72-year-old female with a history of hypertension, lumbar spondylosis, osteoarthritis of the lumbar spine, osteoporosis, and thoracic spondylosis presented to the interventional pain clinic with left-sided thoracic back pain. She rated the pain as 9/10 on the visual analog scale (VAS) prior to undergoing any procedural interventions. The patient had a known L2 vertebral body compression fracture and multilevel lumbar degenerative disc disease at the time of the procedure. The patient had received minimal relief with pharmacologic measures and lumbar level nerve blocks. On April 24, 2019, the patient underwent conventional RFA of the intercostal nerves at the T8-T11 levels but experienced little relief.On February 12, 2020, the patient underwent CRFA of the left intercostal nerve at the levels of T8, T9, T10, and T11 under fluoroscopic guidance. One hundred four days after the procedure, the patient reported 100% improvement in her pain, improving from 9/10 to 0/10, but she reported a new aching, burning, left upper quadrant abdominal pain following the procedure. This developed pain could potentially be peripheral neuritis as a side effect from the CRFA therapy; however, the treatment and the pain are not believed to be linked because the pain was located at a different site than the treatment area, did not overlie sites of RFA intervention, and did not radiate. Since the 104-day post-CRFA follow-up, the patient has not mentioned a change in or return of her thoracic pain.A 31-year-old female with a history of right upper quadrant abdominal pain and mild upper thoracic degenerative disc narrowing presented to the interventional pain clinic with right midback pain. She described the pain as a constant dull ache that radiated to her abdominal right upper quadrant that worsened with coughs and deep breaths. The patient rated the pain as 7/10 on the VAS and said it was tingling in nature. The patient received minimal relief with pharmacologic measures.On May 13, 2020, the patient underwent CRFA of the right intercostal nerve at the levels of T7, T8, T9, and T10 under fluoroscopic guidance. Thirty-five days after the procedure, the patient reported 100% improvement of her pain, improving to 0/10 on the VAS. The patient did not report any negative symptoms. Since the 35-day post-CRFA follow-up, the patient has not mentioned a return of or change in her pain.A 44-year-old male with a history of depression, costochondritis, lumbar facet neuralgia, and intercostal neuralgia presented to the interventional pain clinic with right upper chest and back pain. He rated the pain as 6/10 on the VAS and described it as achy, stabbing in nature, and intermittent. The patient reported that the pain improved with rest and worsened with activity. Pharmacologic and conservative measures provided minimal relief. This patient had received costochondral and trigger point injections from providers outside of the pain clinic. He also underwent right T1-T4 intercostal RFA 16 months prior that he said provided >70% relief. However, the pain returned after 12 months, and the patient re-presented to the pain clinic with chest and back pain.On July 8, 2020, the patient underwent CRFA of the right intercostal nerves at the levels of T1, T2, T3, and T4 under fluoroscopic guidance. Two hundred fifty days following the procedure, the patient reported his pain as 2/10 on the VAS. He did not report any negative side effects from the procedure. Since the 250-day post-CRFA follow-up, the patient has not reported a return of or change in his pain.A 54-year-old male with a history of hypertension, hyperlipidemia, obesity, complex regional pain syndrome, and a compression fracture of the T12 vertebra presented to the interventional pain clinic with right midback pain. The pain radiated around the chest and had been present since the patient fell at work 7 years prior to presentation. The patient rated the pain as 9/10 on the VAS and described it as achy in nature. The patient reported that the pain improved when he lay on his right side and applied ice and heat and worsened with speaking and movement. Pharmacologic and conservative measures did not provide significant relief. The patient had undergone right upper cervical paraspinal trigger point injection; right thoracolumbar paraspinal trigger point injection; right upper trapezius muscle trigger point injections; right costal facet joint injections (T10-T12); denervation of right costal facets with RFA (T7-T9); right C5-C7 RFA; and right C5-C6 transforaminal epidural steroid injection. The patient underwent 2 diagnostic right intercostal nerve blocks prior to CRFA at the levels of T9-T12 that resulted in good relief.On November 11, 2020, the patient underwent CRFA of the right intercostal nerves at the levels of T9, T10, T11, and T12 under fluoroscopic guidance. This patient reported 90% pain relief lasting 334 days and did not mention any complaints about the procedure.A 46-year-old female with a history of migraine headaches, anxiety, depression, xiphoidalgia syndrome, and costochondral junction syndrome presented to the interventional pain clinic with constant epigastric pain. She rated the pain as 5/10 on the VAS with intermittent episodes of shooting pain that reached 10/10. She described the pain as aching in nature and referring from her back to her sternum in a band-shape distribution over her ribs. She reported that the pain worsened with daily activities, talking on the phone, and sitting. The patient received insignificant relief with pharmacologic and conservative measures. She had undergone intercostal nerve blocks that provided moderate, temporary relief from the pain.On November 25, 2020, the patient underwent CRFA of the left intercostal nerves at the levels of T9, T10, T11, and T12 under fluoroscopic guidance. Fifty days after the procedure, the patient reported 75% improvement in her pain but noted that the pain relief provided by CRFA was not immediate; the 75% relief was reached after 4 weeks. Because the pain relief was not 100%, the remaining pain was constant, and the patient continued to experience worsened pain with daily activities, talking on the phone, and sitting. She denied any other negative effects from the procedure. The patient's pain fully returned 7 months after the procedure.A 57-year-old male with a history of hypertension and testosterone deficiency presented to the interventional pain clinic with a diagnosis of intercostal neuralgia at the level of T9 and T10 following a robotic surgery and chest tube placement for thoracic outlet syndrome. He rated the pain as 7/10 on the VAS and displayed 2-point discrimination. The pain referred from the left lower chest around to the abdomen and was associated with allodynia. The pain worsened with light touch and friction from clothing, prompting the patient to lose weight and avoid wearing a shirt while at work. The patient experienced minimal relief with pharmacologic and conservative measures. Intercostal injections did not improve his pain.On February 3, 2021, the patient underwent CRFA of the left intercostal nerves at the levels of T9 and T10 under fluoroscopic guidance. Fifty-five days following the procedure, the patient's pain improved to 2/10 at best and 5/10 at worst. The sensitivity to light touch did not improve with the procedure. Since the 55-day post-CRFA follow-up, the patient has not reported a change in or return of pain.A summary of the 6 cases is provided in the All 6 patients who underwent CRFA to treat their intercostal neuralgia had tried one or more conventional treatments without lasting pain alleviation. The average age of the patients was 50.7 years, and the series included an even number of males and females. We used the average of the pain scores after the procedure to analyze the treatment effect. All 6 patients reported noteworthy pain reduction after CRFA, with an overall average pain reduction of 81.3%. Two patients, both female who presented with thoracic back pain that was not alleviated with NSAIDs and opioids, reported 100% pain relief posttreatment; their CRFA procedures ablated the lower thoracic nerves (T7-T10 and T8-T11).The 2 female patients who experienced 100% pain relief had some key differences in their medical histories. One of the patients was 31 years old, while the other was 72 years. The 31-year-old patient had a minimal medical history beyond her intercostal neuralgia, while the 72-year-old patient had multiple comorbidities. These 2 cases suggest that CRFA for intercostal neuralgia is a potential treatment option for patients with various medical histories and wide age ranges. Common comorbidities were hypertension in 3 patients and depression in 2 patients. Other comorbidities ranged from osteoarthritis of the lumbar spine to migraine headaches.21 so neuropathic pain can develop in other parts of the body. Infection, bleeding, needle placement–induced damage, and burns from grounding pad placement are all adverse effects of thermal lesioning; however, these side effects are rare.22 The prevalence of these side effects associated with CRFA treatment for intercostal neuralgia is not yet known.To our knowledge, this case series is the first to examine the efficacy of CRFA for treating intercostal neuralgia. These 6 patients did not report any side effects related to the procedure other than typical postprocedure soreness that resolved within 2 weeks. After CRFA of the sacral lateral branch nerves, the incidence of postprocedure neuropathic pain is approximately 0.7% per lesion,23 This topic needs further study, specifically for CRFA of the intercostal nerves.The patient in case 3 had the least pain reduction. The patient had previously undergone conventional RFA to treat his intercostal neuralgia and experienced >70% reduction in his pain. His subsequent CRFA procedure resulted in a 66.7% reduction in pain. The decreased reduction in pain after CRFA compared to the original RFA may be attributed to having a second procedure. The efficacy of repeat CRFA can be variable, and patients who undergo 2 or more RFA treatments may have more or less relief after the subsequent treatments. A study assessing the efficacy of radiofrequency medial branch neurotomy for lumbar facet syndrome found similar pain relief with repeat radiofrequency neurotomy compared to the initial procedure.Because of the retrospective nature of this study, postoperative pain assessments were completed after various intervals of time. Treatment plans for patients who undergo CRFA therapy and have a return of intercostal neuralgia symptoms are flexible, with the potential for CRFA therapy to be repeated if sustained pain relief was reported after the first treatment. Additional technologies could also be used, such as spinal cord stimulator and peripheral nerve stimulator therapies; however, treatment decisions require situational discretion and must align with the preference of the patient.24 and intercostal neuralgia is not unreasonably rare. An efficacious treatment modality for intercostal neuralgia could be life-altering for many patients, especially those who are refractory to conservative measures.Patients with chronic pain have a lower quality of life compared to the general population,25 and up to 6 months in the knee,26 so pain relief for patients with intercostal neuralgia could potentially last as long. Further study should be conducted to assess the duration of effect for CRFA for the treatment of intercostal neuralgia specifically and to determine the side effects, ideal candidates, and safety.Because this case series was not standardized, a long-term assessment of these 6 cases cannot be extrapolated. However, studies have demonstrated that CRFA treatment can provide pain relief from 70 to 250 days in the hipThis case series shows that CRFA is a potentially favorable treatment for intercostal neuralgia, resulting in noteworthy reductions in pain. Our findings are consistent with CRFA studies for treating other neuropathies. To further elucidate the safety and efficacy of CRFA for treating intercostal neuralgia and to determine which patients would benefit the most from this treatment, large clinical studies must be conducted.