The results for AP and MMO were based on 3 studies in 39 patients and 4 studies in 50 patients, respectively, all at high risk of bias. The intra-articular administration of MSCs to TMJs, based on weak evidence, may be highly effective in reducing AP and improving MMO. This study received no funding.This systematic review aims to analyze the outcomes of the treatment of temporomandibular joint (TMJ) articular pain (AP) and restricted maximum mouth opening (MMO) with intra-articular administration of mesenchymal stem cells (MSCs). The inclusion criteria allowed primary studies involving AP and/or MMO pre-treatment and post-intervention values. Medical databases that were covered by ACM Digital, BASE, EBSCOhost, Google Scholar, PubMed, Scopus, and Web of Science engines were searched. The risk of bias was assessed with RoB 2 and ROBINS-I tools. The results were tabulated, plotted, and analyzed for regression. A total of 5 studies involving 51 patients/69 TMJs were identified, and 4 studies on 50 patients/67 TMJs were synthesized. Interventions were each time effective in decreasing AP and increasing MMO in a 6-month follow-up period by an average of about 85% and over 40%, respectively. Regression analysis showed a good fit of the logarithmic model for AP relief (5.8 − 0.8 ln x; R Mesenchymal stem cells (MSCs) are stromal cells with a self-renewal potential ,2,3,4. TThe temporomandibular joint (TMJ) actually consists of two separate functional joints due to the existence of an articular disc . The joiTreatment of the progressive degeneration of TMJ is not easy, and therapeutic protocols are still under development. Open access to the TMJ is technically difficult, and even with the use of minimally invasive techniques, there is a risk of serious complications ,31. The It has been proven that MSCs are naturally present in both the cartilage and the synovial fluid of TMJs ,51,52,53The first known article about MSCs transplantation into TMJs was published in 2013 . In its This systematic review aims to identify the clinical trials and cases investigating the treatment of temporomandibular disorders by administering the stem cells into joint cavities and quantitatively evaluating the results of these reports.This systematic review has been developed in accordance with the PRISMA methodology . CheckliThe inclusion criteria allowed the clinical trials and case reports in which treatment of temporomandibular disorders was based on administering autologous stem cells into temporomandibular joint cavities. The effectiveness of the therapy was assessed in the domains of mandible mobility and changes in the intensity of joint pain. Details of the inclusion criteria according to the PICOTS methodology are presented in The searching of medical databases was carried out using four open access search engines: ACM Digital, BASE, EBSCOhost, Google Scholar, PubMed, Scopus, and Web of Science ,69,70,71k). In the event of a discrepancy in the ratings, a given record was transferred to the full-text evaluation. The qualification on the basis of the full content of the reports was made independently by two authors (M.C. and N.T.). In the event of further discrepancies, the third judge (K.C.) had the decisive vote. Data collection was performed independently by two authors (M.C. and N.T.) without the use of automation tools.Reports were selected on the basis of the above-specified inclusion and exclusion criteria. First, the records that were obtained from medical databases were entered into the Rayyan tool . Using tp = 0.05 was adopted. Regression analysis was attempted on the scatter plots. The Google Sheets software  and Microsoft Excel  program was used for visualization and analysis.The following data characterizing the patient groups were extracted from the reports: (1) the number of injections per joint; (2) study group size; (3) the number of females; (4) the number of males; (5) patients’ age; (6) average age; (7) the number of patients that were treated unilaterally; (8) the number of patients that were treated bilaterally; (9) the number of joints treated; and (10) co-interventions. For synthesis and meta-analysis (1) maximum mouth opening (MMO) that was measured in millimeters between the incisors and (2) spontaneous pain on the Visual Analogue Scale (VAS) that was measured before the intervention and during the observation period were extracted from the reports. If the variables were assessed by other scales, the values were not converted. When converting years, months, and weeks into days for the purposes of the analyses, it was assumed that a month consists of 4-weeks. The effects were measured by the differences between the individual values that were expressed in absolute terms and as a percentage of the initial value. The risk of bias for randomized controlled trials was assessed using a revised Cochrane risk of bias tool for randomized trials (RoB 2 tool) . For nonk = 0.83). Ultimately, five studies that were described in five reports were included for the synthesis. Details of the selection process are presented in In total, 332 records were found and 2 of them were deleted in the automatic deduplication process. A manual review of duplicates led to the removal of another 160 items. The remaining 170 abstracts were screened and 11 of them were qualified for full-text evaluation  headache or joint pain (VAS ≥ 4), (2) joint noise and limited mouth opening, (3) patients with previously conservative treatment without symptoms resolution, (4) symptoms lasting for more than 2 years, and (5) MRI that was positive for capsular-ligamentous structures diseases. The study group patients  were treated with arthrocentesis and fat-derived stem cell injections (1 mL). There were seven joints that were treated in total . For 15-days, patients took NSAIDs, followed a bland diet, and did physiotherapy exercises. The control group consisted of four patients treated with saline injections to the upper compartments  underwent arthrocentesis using Ringer’s lactate solution plus intra-articular injection of hyaluronic acid. Patients in the study group  received an injection of 2 mL bone marrow nucleated cell concentrate. The patients returned for follow-up after 1-week, 1-month, 6-months, and 1-year. In both groups, the pain during motion was significantly reduced. After 1-year, the average VAS pain during motion decreased more in the study group than in the control group. The VAS pain at rest also changed from 8.2 to 1.87. The maximum interincisal opening improved after the procedure as well, by 11.8 mm in the study group, and by 4.87 mm in the control group .The article by Mahmmood et al. describes the study involving 11 patients  with temporomandibular disorders. There were six inclusion criteria: (1) clinical diagnosis of anterior disc displacement, (2) limitation in mouth opening, (3) periauricular pain, (4) the presence of symptoms for at least 3-months, (5) clicking, and (6) deviation during mouth opening. The procedure was performed on a single joint in three patients, and bilaterally in eight patients. Before the injection, 8 out of 11 patients presented with pain, and five patients had a problem with limitation in mouth opening. The follow-up period was every 2-weeks for the first 3-months and then monthly. After the 2-weeks, pain disappeared among all the patients and MMO improved (from 28.2 mm to 34.4 mm). There were no significant postoperative complications, apart from mild pain because of the injection and mild bruising on the donor site in one patient. Sembronio et al. reported 40 patients  between 17 and 74 years old. They were randomized into the control group consisting of 20 patients who underwent arthrocentesis with intra-articular injection of hyaluronic acid (HA) and the study group including 20 patients  who received an injection of microfragmented adipose tissue (2 mL) from the abdominal wall. One patient had the harvesting procedure performed in the medial thigh due to a deficiency of abdominal fat. The pain and maximum interincisal opening were evaluated at follow-up examination 10-days, 1-month, and 6-months after the procedure. After 6-months, the pain decreased more in the study group than in the control group. The MIO also improved more in the study group (by 11.7 mm) than in the control group (by 6.2 mm).In the case report that was published by De Souza Tesch et al., a regenerative medicine approach was proposed using in vitro expanded autologous cells from the nasal septum. A 27-year-old male had a severe skeletal Class II and mandibular micrognathia, with an indication of orthognathic surgery for its correction. The CT images showed degenerative changes in both the temporomandibular joints, with intense condylar resorption, especially in the right one. Before the treatment started, the von Korff index for chronic pain severity showed a low pain intensity (<50) without disability (grade I), and the MMO was 23 mm. No complications were reported. After 2 weeks, the MMO improved to 30 mm. After 1-month, the von Korff index of chronic pain severity was zero, and the MMO had a mild decrease to 27 mm. Three months later, the patient still did not feel any pain , and the MMO improved to 31 mm. After 6-months, the MMO improved by 1 mm, and the von Korff index did not change. After 1-year, there were no complaints of pain at rest or during motion, and the assisted MMO reached 36 mm.The risk of bias was assessed for three randomized trials and one non-randomized trial. Each of the studies was characterized by a high risk of bias, which was mainly due to the fact that it was impossible to conceal patients’ membership of the study or placebo group from participants and surgeons delivering the interventions. A detailed assessment is presented in The results of individual studies in the domains of joint pain relief and increasing the extent of mandibular abduction are presented in 2 = 0.90) [The severity of joint pain decreased during the follow-up after the intervention. The data that were needed for this synthesis were provided by the reports by Carboni et al., De Riu et al., and Sembronio et al., whose results appear to be similar ,57,75. F = 0.90) ,57,75. T2 = 0.89)  . The perp = 0.014). [p = 0.045). [The VAS pain values in each of the controlled trials decreased more in the study group than in the control group over the course of 6-months ,57,75. T 0.014). ,57,75. T 0.014). ,57,75. T 0.045). ,57,75. T 0.045). ,57,75.All of the studies that were identified in the course of this systematic review showed a reduction of pain and an increase of the MMO due to the intra-articular injections of stem cells ,57,75,76As shown by the modest results of this review, the injection of autologous stem cells into the cavities of TMJs is not popularly performed. The treatment technique that is used by different researchers differs and it can be assumed that it is at the stage of development ,57,75,76Publications regarding intra-articular injections in the treatment of temporomandibular joint disorders have addressed arthrocentesis and the administration of hyaluronic acid, corticosteroids, blood products, analgesics, and hypertonic dextrose . The effIn this systematic review, we identified only three reports comparing the efficacy of intra-articular administration of MSCs to other injectable therapies ,57,75. ICarboni et al. added that the administration of fat-derived stem cells also improved the morphology of the articular structures that were imaged by magnetic resonance . ComputePossible unfavorable directions for stem cell differentiation, including proinflammatory phenotype-producing pro-inflammatory cytokines, are being cautioned about ,84,85,86MSCs transplantation cannot be treated as a remedy for all ailments that are related to the limited mobility of the mandible. Differential diagnosis takes into account (1) injuries, (2) missing teeth, (3) disturbed occlusive conditions, and (4) excessive muscle tension ,94,95,96Embree et al. discussed the use of resident fibrous cartilage stem cells in cartilage regeneration, which could potentially be used in the treatment of temporomandibular joints . These aOne study was not included in the synthesis as it was a case report and thus did not present a sufficient level of evidence . All of The intra-articular administration of mesenchymal stem cells to temporomandibular joints, based on weak evidence, may be highly effective in reducing articular pain and improving maximum mouth opening in temporomandibular disorders.


Evidence regarding the analgesic effect of distraction through immersion in virtual reality (VR) for care-induced pain has been documented in several phase 2 trials, but comparison with standard treatments in large, randomized studies is needed.In this open-label, multicenter, randomized, phase 3 trial, we evaluated the safety and efficacy of a novel VR therapy solution for distraction in the context of bone marrow biopsy.Bliss is a VR software with 4 imaginary interactive environments in 3 dimensions with binaural sound (head-mounted display). Efficacy regarding pain intensity was evaluated using a visual analog scale  immediately after the biopsy. Secondary end points were anxiety and tolerance. Modified intention-to-treat analysis was performed.P=.26). Concerning anxiety, 67.5%  of the patients were afraid before the biopsy, and anxiety scores were moderate to very high in 26.3%  of the patients before the biopsy and 9.0% (10/114) after the biopsy for all patients, without a significant difference between the 2 groups (P=.83). Immersion in VR was well tolerated by the majority  of patients in the VR group.Overall, 126 patients with previously documented untreated or suspected malignant hemopathy between September 6, 2018, and May 18, 2020, were randomly assigned in a 1:1 ratio to receive pain prevention with a mixture of nitrous oxide/oxygen  or VR (n=63) before and during the bone marrow biopsy. We excluded 8 patients from the final analysis (3 in the MEOPA group and 5 in the VR group). All patients received local anesthesia (lidocaine) before biopsy. Follow-up was limited to 1 month after the biopsy. Participants’ median age was 65.5 (range 18-87) years, and 54.2% (64/118) of patients were male. The average pain intensity was 3.5  for the MEOPA group and 3.0  for the VR group, without any significant differences in age, sex, center, and hemopathy (The intensity of pain did not significantly differ between both arms. VR was well tolerated, and the satisfaction of patients, nurses, and physicians was very high. VR could be an alternative treatment in case of contraindication or intolerance to MEOPA.ClinicalTrials.gov NCT03483194; https://clinicaltrials.gov/ct2/show/NCT03483194 Bone marrow biopsy is a routine procedure for the exploration of hematologic disorders and malignant hemopathies. Biopsy is generally performed on the anterior or posterior iliac crest, and despite local analgesia with lidocaine, the pain level still remains high . A long We conducted an open-label, prospective study between September 6, 2018, and May 18, 2020, in 5 centers in France.The trial was conducted in accordance with the Declaration of Helsinki of 1975, as revised in 2008, and the International Conference on Harmonization Good Clinical Practice guidelines for biomedical research. The “Sud-Méditerranéen I” Regional Ethics Committee approved the study on February 14, 2018 (2017-A02701-52), and the Agence Nationale de Sécurité du Médicament approved it on March 9, 2018. All patients provided written informed consent.3, and use of certain drugs . We also excluded patients for whom MEOPA was not recommended  and those in whom 3-dimensional movies (pacemaker or defibrillator) were contraindicated.Eligible patients were aged 18 years and older with previously documented or suspected untreated malignant hemopathy with an indication for a bone marrow biopsy. An Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2 and normal biological coagulation parameters were required. Clinical examination and bone pelvic imaging were performed before inclusion to exclude iliac lymphoma localization. The exclusion criteria were pregnancy, congenital or acquired coagulation deficit, thrombocytopenia less than 50,000/mmRandomization was planned by minimization upon inclusion of patients in the study and programmed using ENNOV clinical data management software . Patients were randomly assigned 1:1 to a pain prevention program using MEOPA or VR. Treatment allocation was stratified by center, age, sex, and hemopathy. In case of intolerance in the VR arm, a change to MEOPA was permitted.The primary endpoint was a pain reduction of 1.5 points on the VAS for patients included in the VR group in comparison with the MEOPA group. The secondary objectives were the number of lidocaine vials used; duration of exposure to MEOPA ; tolerance of the VR session; anxiety level before and after the biopsy; sense of presence for the VR arm; level of residual pain and memory of pain after 1 month of follow-up; and assessment of patient, nurse, and physician satisfaction.All patients were lying face down with their hands positioned under the head (based on the French Society of Hematology guidelines) . Local aIn the MEOPA group, administration was started at the same time as the local anesthesia. In the VR group, a 5-minute demonstration session was proposed on the day of randomization to assess tolerance before the biopsy, and the program was started 5 minutes before anesthesia with a maximum duration of 40 minutes. In cases of intolerable pain during the procedure, salvage treatment with a second local injection of lidocaine and/or paracetamol (1 g) or alprazolam (0.25 mg) was proposed.Bliss is a type 1 medical device with European accreditation . It is a 3-dimensional interactive VR application. The program runs on a smartphone and a GearVR head-mounted display. We proposed 4 imaginary VR environments with a median duration of 15 minutes to 40 minutes: Nohara , Kaitei (seabed exploration), Uchuu , and Mori  and the adapted Spielberger State-Trait Anxiety Inventory (STAI) form Y before and 15 minutes after the biopsy . The STAThe level of residual pain and the memory of pain were assessed by the investigators 1 month after the biopsy .The primary end point was to measure the intensity of pain in each group using the VAS and to demonstrate a 1.5-point reduction in pain in the VR group. We enrolled 120 patients to validate this hypothesis with an SD of 2.5, power of 90%, and type I error rate of 5%. We included 6 more patients, considering that 5% could not be evaluated using 2-tailed tests. Intention-to-treat analysis included patients for whom pain assessment was available.t test was used to compare quantitative data, and the chi-square test or Fisher exact test was used to assess qualitative data. Correlation analysis was performed using the Spearman test.Variables are presented in tables; the Student All statistical analyses were conducted using SAS 9.3 software (SAS Institute Inc) with a significance of 5%.A total of 126 patients were enrolled between September 6, 2018, and May 18, 2020, in 5 centers in France: Le Mans (n=80), Strasbourg (n=32), Bordeaux (n=8), Saint-Mandé (n=5), and Angers (n=1). Trial recruitment stopped after inclusion of the target population. We excluded 3 patients before randomization , and 5 patients were excluded after randomization from the final analysis (intensity of pain not documented: 4 patients in the VR group and 1 patient in the MEOPA group). An additional 3 patients did not complete the VR session in the VR group: 1 patient refused VR after the short demonstration and then also refused MEOPA, 1 patient was intolerant, and 1 patient experienced unbearable anxiety. The 2 latter patients both received MEOPA during the biopsy. They were excluded from the per-protocol analysis but included in the intention-to-treat analysis .P=.68) and sex (P=.84). Lymphoma and myeloproliferative disorders were the most common diagnoses . Blood pressure was recorded for 116 patients before the biopsy  and 92 patients after the biopsy . The demographics and patient characteristics are shown in The median age of the study population was 65.5 (range 18-87) years, and 54.2% (64/118) were male. Most  of the patients were ECOG 0-1. The 2 groups were equally balanced in terms of age (P=.45) and 55.4% (52/118) of patients 15 minutes after the biopsy . A median of 1 vial of lidocaine was used for local anesthesia ; 24 patients received 2 or more vials of lidocaine , and none received oral salvage treatment  was documented in 59.4% (63/118) of patients before biopsy  to assess their tolerance. During the VR demonstration, most  of them watched the entire session, while 2 patients stopped the session: The first patient felt intolerance during the demonstration, and the second patient finally refused VR after completing the demonstration session without an adverse event  of patients felt immersed during the VR session, 73% (41/56) felt elsewhere, and 66% (37/56) felt like they were in a dream (Table S3 in P=.27), and the median pain was 3.0 in both groups (P=.51). One-quarter  of the patients retained a memory of pain experienced during the biopsy at 1 month , with a median score of 3.0 on the VAS . There were no significant differences by age, group, sex, hemopathy, and centers.Pain after biopsy was evaluated using 3 questionnaires: intensity with the VAS 15 minutes after the procedure, residual pain, and memory of pain 1 month after the procedure. In the intention-to-treat analysis with the last available information carried forward, the average pain was 3.5 (SD 2.6) and 3.0 (SD 2.4) in the MEOPA and VR groups, respectively . Among them, 67.5% (79/117) were afraid of the biopsy, with a median score of 5.0 . The causes for fear were the local injection of lidocaine in 40% (32/79) of cases, biopsy in 91% (72/79), and biopsy results in 73% . Of the patients, 26.3% (30/114) were anxious, with a score over 46, before the biopsy, and 9% (10/114) of patients were anxious after, without any significant difference between the MEOPA and VR groups (P>.99).The STAI questionnaire was completed by 114 patients. The theoretical range of scores is from 20 to 80 points: the higher the score, the more anxious the patient. The median score was 38 (range 20-73) and 32 (range 20-65) before and after the biopsy, respectively, for all patients, without any significant differences between the 2 groups ; the technique was recommended by 97% (56/58) of the MEOPA group and 90% (52/58) of the VR group (P=.13).Satisfaction with the relaxation method was experienced by 98.3% (114/116) of patients, without a significant difference between the 2 groups (P=.03); pain was reported by 77.1% (43/116) of cases , and stress was reported by physicians for 15.5% (18/116) of cases . They observed crying in 6.9% (8/116) of patients  and global satisfaction with the method in 95.7% (111/116) of cases .According to the nurses, the method was technically binding for 34.4% (40/116) of the cases  of cases. They recognized pain in 49.6% (58/117) of patients: 59% (35/59) of the MEOPA group and 40% (23/57) of patients in the VR group (P=.18). They felt relaxed during the biopsy of 88% (52/59) of cases in the MEOPA group and 93% (54/58) of cases in the VR group (P=.21). They were satisfied with the relaxation technique with 95.7% (112/117) of cases  and recommended reuse of the method with 94.0% (110/117) of cases .According to the physicians, MEOPA was easy to use in 78% (46/59) of cases, and VR was easy to use in 79% . Anxiety scores and blood pressure were not statistically different between the 2 arms, both before and after the biopsy. Patients, nurses, and physicians were very satisfied with the relaxation method, without significant differences between VR and MEOPA.REVEH is the first randomized study to compare VR with standard MEOPA in preventing pain during bone marrow biopsy. The intensity of pain did not significantly differ between VR and MEOPA: 3.0 versus 3.5 ; a new generation of head-mounted displays has recently emerged with full smartphone integration to facilitate set-up and reduce start-up time (not investigated in this study). Only bone marrow biopsy was evaluated; the impact of VR in the same context should be evaluated for other procedures . We do not know if the patients had already been exposed to VR during their leisure time . Patient choice of the scenario was not recorded in this study, so programs were not compared with each other. Patients also could not compare them from one procedure to another (only 1 biopsy per patient). Pain and anxiety are very subjective symptoms that vary from patient to patient and are influenced by the self-experience. Physiological markers  to objectively assess pain and anxiety have been published: blood pressure and heart rate variations, pupil reflexes, stress hormonal changes, electro-encephalography, magnetic resonance imaging, and positron emission tomography to assess brain activity . These pEven if the primary outcome of the study has not been achieved, the VR-based relaxation method was well tolerated, and the satisfaction of patients and physicians was very high in the VR group. In the future, the patient will put the helmet on himself or herself and choose his or her own program; in contrast to the use of analgesics or sedatives, no medical monitoring is indicated during and after the procedure, and driving is allowed. The length of time that the patient must be present will be shorter, with a probable socioeconomic impact, which will have to be evaluated.Several meta-analyses were published between 2019 and 2020 that evaluated the impact of VR on fatigue, anxiety, depression, and care-induced pain -34. BasePain intensity did not significantly differ between VR and MEOPA arms during bone marrow biopsy in this study. The VR-based distraction method was safe and appreciated by patients and caregivers. Digital therapeutics could be an alternative treatment in case of contraindication or intolerance to MEOPA and could be integrated into the oncology support care panel.Further studies should focus on demonstrating the efficacy of a VR program  in pain prevention and other symptoms  for each indication, compared with conventional drugs with a noninferiority outcome, if possible, and based on feasible objective parameters. The impact of VR will also have to be studied for patients hospitalized for a long period of time and at home for outpatients. For chronic pain, VR should be evaluated in terms of scheduling, efficacy, and tolerability to reduce opioid dependence in cancer patients -39. Phar


ObjectivesThe objective of the study was to determine the effect of a single dose of IV dexamethasone on postoperative pain in patients after laparoscopic cholecystectomy. The outcome will be measured in the terms of mean pain score.Study design and settingThis is a prospective study. We did a randomized control trial to compare the outcome in two groups. This study was conducted in the Department of Surgery, Benazir Bhutto Hospital, Rawalpindi, from December 2021 to May 2022. The total duration of the study was six months.MethodologyA total of 160 patients were randomly divided into group A and group B. We performed laparoscopic cholecystectomies on all the patients under standard general anesthesia. In group A (control group), 5 mL of normal saline was injected intravenously at the time of induction of anesthesia. In group B, the dexamethasone group, the inj. dexamethasone with a dose of 0.1 mg/kg diluted in 5 mL normal saline was given intravenously at the time of induction of anesthesia. Postoperatively, the median pain score was measured using visual analog scale (VAS) at 2, 6, 12, and 24 h on a specially made proforma. The results were further stratified according to gender and age.ResultsThe postoperative VAS in group B was significantly low compared with group A when measured at 2, 6, 12, and 24 h. It means that the median pain score was markedly less in the study group than in the placebo one, and it was statistically significant (p<0.05).ConclusionAdministration of a single dose of dexamethasone preoperatively in laparoscopic cholecystectomy patients is effective to control postoperative pain. Gallstones are present in up to 20% of the population, with their percentage slightly higher in females . Gall bl2), peritoneal inflammation, and peritoneal stretching due to pneumoperitoneum. Medical practitioners have advised and used various techniques to minimize this, like preoperative administration of opioids or opioid-sparring analgesia, clonidine, preoperative pregabalin, wound site instillation of local anesthetics, and intraperitoneal irrigation with bupivacaine or ondansetron and suctioning of residual gas from the peritoneum before closure [There are various explanations to post LC pain. However, the most accepted reasons are peritoneal irritation due to carbon dioxide  of 1.94, test value of the population mean pain score of 4.03, and an anticipated population mean pain score of 3.03. A consecutive non-probability technique was used to select the patients while ensuring double-blinding. Patients of both genders aged 25-55 years undergoing elective laparoscopic cholecystectomy for cholelithiasis were included in this study. On the other hand, patients who were immunocompromised or had any chronic illness like diabetes mellitus (DM), ischemic heart disease (IHD), chronic kidney disease (CKD), chronic liver disease (CLD), any previous history of radiotherapy or chemotherapy, history of chronic pain of more than three months, any previous hepatobiliary surgery or who had laparoscopic cholecystectomy converted to open were excluded from this study.Before surgery, we measured blood sugar levels (random) and other baseline investigations like complete blood count, blood urea/sugar, and hepatitis screening in addition to a preanesthesia workup. Cholelithiasis was confirmed on abdominal ultrasound. Formal approval was taken from the Research and Ethical Committee, Rawalpindi Medical University and Allied Hospitals, Rawalpindi with approval no. 294\IREF\RMU\2021. After approval, a total of 160 patients were admitted through the outpatient clinic of Benazir Bhutto Hospital Surgery Department as elective cases.A total of 160 healthy and competent patients were recruited. The first author took thorough informed consent and then used concealed envelopes to allocate them to the two groups. The first author informed the anesthetists to administer the drug or placebo. Anesthesia notes were hidden from the patient and the assessors of pain who were the second author and the doctors of the surgical unit. All patients were given PO midazolam 7.5 mg orally the night before surgery. Appropriate intravenous antibiotic (inj. cefuroxime 1.5 g) prophylaxis was given to all patients within 60 min before the skin incision and another dose 6 h after surgery. All surgical procedures were performed under general anesthesia using endotracheal intubation (for controlled ventilation) and a combination of sevoflurane , propofol (IV anesthetic), fentanyl , and atracurium (muscle relaxant). In group A (control group) 5 mL of normal saline was injected intravenously at the time of induction of anesthesia. In group B, the dexamethasone group, dexamethasone with a dose of 0.1 mg/kg diluted in 5 mL normal saline was given intravenously at the time of induction of anesthesia. After the surgery, the gas in the peritoneal cavity was thoroughly evacuated from the port sites. On the first postoperative day, all patients were given three doses of ketorolac 30 mg IV  and Zantac 50 mg IV (H2 receptor blocker). All patients received the same level of care and were assessed for postoperative pain at 2, 6, 12, and 24 h by VAS. The on-call doctors assessed pain and documented it on the attached proforma in patients' notes along with the need for rescue analgesia. They gave the patients a dose of 75 mg of Dicloran IV as rescue analgesia when the pain score was >5 on VAS [Data were analyzed using SPSS, version 21 . Means/medians and standard deviations were calculated for quantitative data like age and pain scores. We used frequency and percentage for the analysis of qualitative data like gender. VAS were compared between groups by independent sample t-test. Effect modifiers like age were controlled by stratification. Poststratification independent sample t-test was applied. A p-value <0.05 was considered statistically significant.We included 160 patients in the study. The patients were divided into groups A and B, with 80 patients in each. The mean age of the patients was 40.38±9.59 years. The age range was 25-55 years. There were 66.9% (n=107) female and 33.1% (n=53) male patients. All the patients were stratified according to age group; 45.6% (n=73) patients were 40 years old or less, while 54.4% (n=87) patients were above 40 years of age. These distributions can be seen in Figures We compared the median pain score between the two groups according to VAS at 2, 6, 12, and 24 h after the completion of surgery between the two groups. The results depicted a statistically significant difference in the pain score of the two groups at 6, 12, and 24 h after surgery. However, there was no significant difference in pain scores between the two groups, 2 h after surgery (p=0.054) (Table The mean pain score was also compared by applying a t-test after stratification according to the age and gender of the patients. The age groups did not have a statistically significant difference but both genders had a statistically significant difference in pain scores at 2, 6, 12, and 24 h after surgery. The males had low VAS compared to females when assessed at each time interval. This is evident in Tables Laparoscopic cholecystectomy is the standard operative intervention for symptomatic cholelithiasis. The advantages of laparoscopic surgery over conventional open surgery are immense. This is due to less postoperative pain, shorter length of hospital stay, early return to the job, and decreased morbidity of the patients. Though there is an established superiority of laparoscopic cholecystectomy over open cholecystectomy, there are specific concerns about the procedure, with postoperative pain being the most important . The typIn our study, the role of dexamethasone in reducing postoperative pain was evaluated. There are various studies present in the literature about the same subject. In a study done by Mohtadi et al., the role of dexamethasone in reducing postoperative pain was studied . In thatIn another study by Lim et al., the role of dexamethasone in reducing postoperative pain and its timing of administration were studied . There wIn a double-blinded trial conducted by Sánchez-Rodríguez PE et al., they measured the effect of IV dexamethasone against a placebo, given preoperatively to patients who were listed for laparoscopic cholecystectomy . They meWhile most of the studies found in the literature affirm our study's results, a few studies show no significant difference in postoperative pain in the patients who were given dexamethasone preoperatively. A similar study was done by Gul et al. that showed that dexamethasone has a role in reducing postoperative pain, analgesia requirement, nausea, and vomiting . HoweverThe role of dexamethasone is well-established in reducing postoperative pain in laparoscopic cholecystectomy as well as other laparoscopic surgeries. The results of our study further strengthen this fact. Additional benefits may include decreased postoperative nausea and vomiting.There are a few limitations to our study. This study was conducted in a single center, and the sample size was small. Further, we have administered rescue analgesia at a VAS of 6 or more, whereas most literature indicates that rescue analgesia should be administered at VAS greater or equal to 4. It is likely to affect the total analgesia consumed. Our recommendations are to conduct this study on a larger scale to produce statistically more significant results to make this technique more useful in the future to control postoperative pain.In our study, we have successfully demonstrated that the administration of a single-dose injection of dexamethasone before induction of anesthesia significantly reduces postoperative pain after laparoscopic cholecystectomy. Good pain management leads to early recovery and short hospital stays which not just provide mental relaxation to hospital staff but also financial assistance to the trust. So, we recommend that dexamethasone is a safe and efficacious drug to reduce postoperative pain.


Neuropathic pain is common in cancer survivorship and is one of the most distressing symptoms for patients previously treated for head and neck cancer. Persistent neuropathic pain, when it is ongoing and uncontrolled, has a detrimental effect and erodes patients’ quality of life. Patients treated for head and neck cancer are chronic opioid users to manage their post-treatment pain, which may entail an increased risk of addiction and overdose. We propose to evaluate the analgesic activity of high-concentration capsaicin patches for the treatment of head and neck cancer survivors presenting with neuropathic pain sequelae.TEC-ORL is a parallel, multicenter randomized comparative phase II study evaluating whether Capsaïcin patches (Qutenza®) reduce neuropathic pain when compared to Amitriptyline (Laroxyl®) in head and neck cancer survivors presenting with neuropathic pain sequelae. The primary efficacy outcome is the rate of patients with a pain reduction of at least two points at 9 months compared to baseline. Assuming that 5% of patients become lost to follow-up, 130 patients will need to be randomized to detect a 25% improvement  using a one-sided chi-square test with an alpha of 0.05%. According to the recommendations for comparative phase II trials, the target differences and type I error rates are relaxed. Randomized patients will either be treated with a capsaicin 8% (Qutenza®) patch applied at three time intervals in the experimental arm or with Amitriptyline (Laroxyl®)  taken for 9 months at the recommended daily dose of 25 mg to 75 mg in the control arm.TEC-ORL is a randomized comparative phase II trial designed to comprehensively evaluate the analgesic activity of capsaicin compared to Laroxyl in Head and Neck Cancer survivors presenting with neuropathic pain sequelae.NCT04704453 Date of registration: 2021/01/13.ClinicalTrials.gov identifier:  After curative cancer treatment, pain may affect up to 40% of cancer patients in remission . In the A recent study highlights that 50% of patient’s treated for head and neck cancer are chronic opioid users to manage their post-treatment pain , which mGiven that capsaicin treatment of the head and facial region has proven to be feasible albeit with specific warning and precaution caveats, our hypothesis is that high-concentration capsaicin patches reduce neuropathic pain when compared to Amitriptyline (Laroxyl®) in head and neck cancer survivors presenting with neuropathic pain sequelae.The primary objective of this study is to evaluate whether Capsaïcin patches (Qutenza®) reduce neuropathic pain when compared to Amitriptyline (Laroxyl®) in head and neck cancer survivors presenting with neuropathic pain sequelae.Secondary objectives include a sensitivity analysis, the evolution of neuropathic pain, the safety and health related quality of life.This is a Phase II, multicenter, randomized open-label and comparative study designed to evaluate whether Capsaïcin patches (Qutenza®) reduce neuropathic pain when compared to Amitriptyline (Laroxyl®) in head and neck cancer survivors presenting with neuropathic pain sequelae . The primary endpoint is pain evaluated using a numeric scale. We opted for a randomized comparative phase II trial design rather than a single arm or a randomized non-comparative phase II trial to avoid obtaining false positive or false negative results only related to the study hypothesis . All heaThe primary efficacy outcome is the rate of patients presenting a pain reduction of at least two points at 9 months compared to baseline. Pain will be evaluated using a numeric scale from 0 (No pain) to 10 (Worst pain) by considering the average pain in the last 24 hours. Modification of a pain treatment strategy will be considered as a failure if the modification relates to neuropathic pain. Pain treatment modifications that are not related to neuropathic pain and missing values will not be considered as a failure.The sensitivity endpoint is defined as the rate of patients presenting a pain reduction of at least two points at 9 months compared to baseline. Modification of the pain treatment strategy for any reason or patients with missing values will be scored as a failure*.Neuropathic pain will be evaluated using the French language Neuropathic Pain Symptom Inventory (NPSI) which was developed and validated in that language . The NPSSafety will be assessed using the toxicity grading of the National Cancer Institute (NCI-CTCAE v5).Quality of life will be evaluated with the EORTC QLQ-C-30 questionnaire.After giving their written informed consent, patients which satisfy all the inclusion and non-inclusion criteria Table  will be Patients randomized to the control arm will be treated with Amitriptyline (Laroxyl®)  taken for 9 months at the recommended daily dose of 25 mg to 75 mg.Patients randomized to the experimental arm will be treated by application of an 8% capsaicin patch (Qutenza®) at three time intervals: the first application within two weeks of randomization and the next two applications at three monthly intervals.Patients will be followed-up every 3 months from the date of randomization. Assessments will include, clinical examination, pain evaluation using the numeric scale (primary endpoint), quality of life evaluation based on the EORTC QLQ-C30 questionnaire and neuropathic pain evaluation with the NPSI. Any adverse events (AE) related to the study treatments will be collected until completion of the study.Patient data will be collected by the investigator (or representatives) via an electronic Care Report Form (e-CRF) provided by the Institut Claudius Regaud Data Management Department. The e-CRF is based on ENNOV Clinical® software edited by Ennov Company. It is available on the secure website. Study data validation will be carried out to verify the completeness, the accuracy and consistency of data collected in the e-CRF. Data clarification forms will be issued by the Data Management Department of ICR in order to allow investigators sites to resolve data deficiencies and/or in accuracy.Based on the literature, we expect 25% of patients to present with a pain decrease of at least two points . To deteThe primary endpoint will be analyzed on the Intent To Treat population and expressed as values and percentages with 95% one-sided confidence intervals. Treatment effect will be estimated using a logistic regression model adjusted for stratification factors . Odds raAs the population of head and neck cancer survivorship increases, it has become increasingly important for health care providers to propose an optimized treatment for neuropathic pain. There is an unmet need for well-designed, robust clinical trials to help improve therapeutic strategies in this setting. Single arm trials, introduce several forms of bias including patient selection, and misspecification of the hypothesis. We therefore opted for a randomized comparative phase II TEC-ORL trial design. Randomized comparative trials are an essential tool to evaluate therapeutic strategies and new treatments. However, designing and conducting a randomized trial on supportive care for neuropathic pain is associated with several challenges . SeveralNeuropathic pain is common in cancer survivorship and is one of the most distressing symptoms for patients previously treated for head and neck cancer. Neuropathic pain also decreases quality of life. There is a need to provide optimal first-line treatment to reduce neuropathic pain and to limit chronic opioid use for post-treatment neuropathic pain management . To the


IntroductionWith the rising number of arthroscopic partial meniscectomy and meniscus repair procedures performed in outpatient surgical centers, there has been significant interest in limiting postoperative pain and optimizing recovery. Postoperative pain is a common reason for admission at these surgical centers, and opioid-related mortality is becoming an increasing concern. A surgeon-performed saphenous nerve block (SNB) represents a promising adjunct treatment option for pain control. The purpose of this randomized controlled trial was to determine if an SNB would result in decreased postoperative pain and opioid usage compared to control following arthroscopic meniscus repair or partial meniscectomy.MethodsWe randomized patients between two groups: one receiving an SNB and the other without an SNB. The operating surgeon performed the SNB using a landmark-based approach at the medial femoral epicondyle/adductor hiatus with 5 mL of 1% lidocaine preoperatively and 5 mL of 0.5% ropivacaine postoperatively. Neither ultrasound nor nerve stimulator was utilized to confirm the success of the block. The visual analog scale was utilized to record pain preoperatively and in the immediate postoperative period, one day, and seven to 10 days postoperatively. The nursing staff in the post-anesthesia care unit monitored patient pain levels and provided pain medication accordingly.ResultsWe enrolled 80 patients, with 40 patients in each group. There was no difference in age, sex, body mass index, or laterality between study groups. Overall, there were no differences between groups in preoperative or postoperative pain at any time. The average pain scores preoperatively were 2.78 in the experimental group and 3.05 in the control group (p=0.502). In the immediate postoperative period, pain scores were 1.57 for the experimental group and 2.66 for the control group (p=0.090). No statistically significant difference was detected in the number of patients requiring opioids postoperatively or in the morphine milligram equivalents (MME) provided to patients receiving opioids. Twelve patients in the experimental group received opioids in the immediate postoperative period while 18 patients in the control group received opioids (p=0.248). We observed no adverse events in patients from either group.ConclusionAs a pure sensory nerve, the saphenous nerve is an excellent target for pain control without associated leg weakness. We utilized a low-resource SNB in knee arthroscopy for partial meniscectomy and meniscus repair as an adjunct therapy for postoperative pain control. This randomized controlled trial suggests that surgeon-performed blocks via a landmark-based approach are not effective in controlling pain or limiting opioid use in the immediate postoperative period. However, given our lack of confirmatory testing via ultrasound or nerve stimulation, a true nerve block may not have been achieved in all patients. We believe this adds to the external validity of this study, as these tools may not be readily available in all settings. Arthroscopic knee surgery is routinely performed on an outpatient basis, and these cases contribute to a large portion of the volume at ambulatory surgery centers . Pain coIn 2009, Volkow et al. found orthopedic surgeons to be responsible for 7.7% of all opioid prescriptions, however, in more recent years, Medicare trends suggest a decrease in opioid prescriptions by orthopedic surgeons -7. As awWith regards to nerve blocks for pain control in knee arthroscopy, researchers have described techniques for blocks of the femoral, sciatic, obturator, and saphenous nerves, mainly through the assistance of ultrasound or a nerve stimulator -14. In 2We identified the SNB as an effective alternative form of pain control for knee arthroscopy based on our literature review. However, compared to previous studies, we wanted to evaluate a low-resource landmark-based approach to the SNB without confirmatory ultrasound or nerve stimulator against a simple postoperative portal site injection of local anesthetic. We hypothesized the landmark-based approach to an SNB would result in decreased immediate postoperative pain scores as well as decreased opioid use in the immediate postoperative period when compared to patients receiving only local anesthetic at the portal sites.After obtaining approval from the institutional review board at Thomas Jefferson University , we conducted a randomized control trial with two groups: patients receiving an SNB in the experimental group and patients not receiving an SNB in the control group. We selected patients 18 years or older with the ability to consent to the research protocol undergoing meniscus repair or partial meniscectomy at one of our ambulatory surgical centers and excluded those who had prior open or arthroscopic surgery on the ipsilateral knee. Data collection occurred at ambulatory surgical centers owned by a single, private institution with operations performed by two fellowship-trained sports surgeons. We followed the recommendations found in the CONSORT 2010 statement in reporting this study .After induction of general or sedation anesthesia and prior to portal placement, the primary surgeon performed an SNB with 5 mL of 1% lidocaine by a landmark-based approach at the medial femoral epicondyle/adductor hiatus for the experimental group. The control group did not receive an SNB. The surgeon also injected 5 mL of 1% lidocaine without epinephrine into each of the proposed portal sites for both groups. They performed the remainder of the procedure identically between the two groups, and after surgery, they injected 0.5% ropivacaine at the portal sites for both the control and experimental groups until a wheel was formed. The study group also received a final injection of 5 mL of 0.5% ropivacaine into the region of the saphenous nerve as described above.Our primary outcomes were the immediate postoperative pain level by visual analog scale (VAS) and postoperative opioid use, and our secondary outcomes were postoperative Day 1 and Day 7 to 10 VAS. The primary surgeon obtained preoperative, immediate postoperative, one-day postoperative, and seven to 10-day postoperative pain levels by VAS. The nursing staff in the post-anesthesia care unit offered the patients pain medication and provided the medication per the patient's request. We converted postoperative opioid use into MME.Our power analysis prior to the initiation of the study suggested that 160 subjects would be required to detect a meaningful difference in the VAS pain scale with a power of 80% and a significance level of p = 0.05. This analysis assumed a VAS pain score of 3.5 ± 2 in the SNB group based on previous studies -14. We aAll statistical analyses were done using R Studio . P-values for continuous data were calculated by t-tests or Mann-Whitney tests, and p-values for categorical data were calculated by chi-square or Fisher’s exact tests.We recruited patients from January 2021 to April 2022 and recruitment was stopped early after the results of a preliminary statistical analysis with 80 patients. All 80 patients received their intended treatment with 40 in each group, and all patients were included in the final analysis.The patients in the experimental group were not statistically different from the control group Table  with regOn average, the patient-reported preoperative pain scores by VAS were 2.78 in the experimental group and 3.05 in the control group (p=0.502). In the immediate postoperative period, the patients in the experimental group rated their pain at 1.57 on average while the patients in the control group rated their pain as 2.66 on average (p=0.090). We identified no statistically significant difference in pain scores between the groups, including Day 1 (p= 0.331) and Days 7 to 10 (p=0.561) pain scores  to make a conclusion without committing type I or type II errors with regard to the immediate postoperative pain score. An additional 134 patients (67 per group) would be required for the same reasons to make a conclusion regarding the MME provided.As a pure sensory nerve, the saphenous nerve represents an excellent target for pain control without associated leg weakness . Prior rOur study is different in that we have a larger study population of 80 patients, and our SNB was performed without confirmatory testing by ultrasound or nerve stimulation. Thus, representing a more feasible option in resource-limited settings and a less time-consuming process. It is our experience that the block performed in this study had a negligible effect on the operative time, with each block taking less than one minute to perform. Additionally, no training beyond that received in our fellowships was needed to perform this block. In 2005, Benzon et al. described a technique for an SNB at the medial femoral condyle by injecting an anesthetic in a fan-wise direction between the skin and the periosteum of the medial condyle . Kent etThe immediate postoperative pain scores by VAS in our study were low in comparison to these similar previous studies at 1.57 and 2.66 in the experimental and control groups, respectively. Akkaya et al. found postoperative pain scores of 3.15 and 5.25 in their SNB and control groups, respectively, and the postoperative pain scores in the study by Hsu et al. were 3.3 and 4.5 for the SNB and control groups, respectively -14. HoweApart from patient satisfaction with decreased pain, one of our primary goals was to utilize the SNB to reduce postoperative opioid use. Researchers in previous studies were inconsistent with regard to the efficacy of the SNB in reducing opioid consumption. Akkaya et al. utilized patient-controlled anesthesia with tramadol and identified decreased tramadol use in their nerve block cohort over the first 24 hours after surgery . In our We made the decision to stop recruiting patients early because of the infrequency at which opioids were provided and the minimal differences between MME provided between our two groups. Our preliminary analysis suggested that more patients would be required than described by our original power analysis, and we believe this is related to the decreased accuracy of a landmark-based approach to SNB as well as the efficacy of the postoperative portal site injections in controlling pain.Our limitations include the early cessation of recruitment, the lack of surgeon blinding to patient allocation, the decreased success rate of a landmark-based approach to the SNB, no strict protocol for postoperative pain management, outpatient surgery setting, the inherent variability of pain scores, and recruitment at a single-center by two surgeons. However, we intended to sacrifice the internal validity of the study with a less strict protocol to improve the generalizability of our findings.Our study is the largest to date evaluating the efficacy of an SNB for arthroscopic knee surgery. These data suggest that the addition of an SNB without image guidance or confirmatory testing to a simple postoperative portal site injection of local anesthetic offers no benefit to postoperative pain scores or opioid use. We did not include information regarding long-term follow-up of patients receiving an SNB, and thus we cannot assess for complications beyond one week or variations in long-term patient outcomes.


Subgrouping of migraine patients according to the pain response to manual palpation of the upper cervical spine has been recently described. Based on the neuroanatomy and the convergence of spinal and trigeminal nerves in the trigeminocervical complex, the cervical segments C1 to C3 are potentially relevant. To date it has not been investigated whether palpation results of all upper cervical segments are based on one underlying construct which allows combining the results of several tests. Therefore, the aim of this secondary analysis of a cohort study was to determine whether results from all three segments form one construct.Seventy-one migraine patients with chronic or frequent episodic migraine diagnosed according to the international headache society classification version 3 were examined by one physiotherapist. Manual palpation using a posterior to anterior pressure was performed on the upper three cervical vertebrae unilaterally left and right. The results of the palpation according to the patients’ responses were combined using factor analysis. In addition, item response theory (IRT) was used to investigate the structure of the response pattern as well as item difficulty and discrimination.Factor analysis  showed that the palpation of C3 loads less onto the underlying construct than the palpation of C1 and C2. Considering a cut-off value > 1.0, the eigenvalues of all three segments do not represent one underlying construct. When excluding the results from C3, remaining items form one construct. The internal consistency of the pain response to palpation of C1 and C2 is acceptable with a Cronbach’s alpha of 0.69. IRT analysis showed that the rating scale model fits best to the pain response pattern. The discrimination value (1.24) was equal for all items. Item difficulty showed a clear hierarchical structure between the palpation of C1 and C2, indicating that people with a higher impairment are more likely to respond with referred pain during palpation of C2.Statistical analysis confirms that results from the palpation of the cervical segments C1 and C2 in migraine patients can be combined. IRT analysis confirmed the ordinal pattern of the pain response and showed the higher probability of a pain response during palpation of C2. The pain response to C3 palpation is not relevant for unidimensional IRT analysis.https://www.drks.de/drks_web/setLocale_EN.doGerman registry of clinical trials (DRKS00015995), Registered 20. December 2018,  Migraine patients showed significantly more musculoskeletal findings in the cervical spine (Cx) compared to a control group without headaches . The so-The presence of additional neck pain is associated with a more severe clinical presentation in migraine patients and a delayed response to pharmacological therapy , 5. Migrno pain responselocal pain provocationpain radiating into the typical headache areaTherefore, palpation of the upper cervical spine might be a suitable test for distinguishing migraine patients from healthy individuals and previous work has shown that migraine patients can be stratified into three groups based on pain provocation :no pain These results indicate that there are potentially different underlying pathophysiological phenomena within the migraine population, in which presumably the influence of the cervical spine on migraine symptoms is either particularly strong, possibly strong, or not existing. Analogous findings have also been described in previous studies . To straHowever, all previous studies have focused on the vertebrae C0-C2  of the upper cervical spine. Ignoring C3 , might provide misleading results. Anatomically, the nucleus trigeminus spreads as far caudally as C3. Based on the neuroanatomical relationship described above, all segments including C3 should be assessed. Structures that are capable to produce referred pain to the head are innervated by C1, C2 and C3 spinal nerves . To deteMethods in detail are described elsewhere . In brieParticipants had to have chronic or frequent episodic migraine diagnosed by physicians at the Headache Outpatient Clinic of the University Medical Center Hamburg Eppendorf using the IHS  third edition criteria . In the Patients who had a diagnosed pathology of the cervical spine with existing symptoms or a history of trauma  to the cervical spine were excluded. Furthermore, patients during pregnancy or lactation were excluded. Patients were not allowed to have a medically relevant internal, psychiatric, or neurological disease that could have affected pain perception. Patients with alcohol and/or substance abuse in their medical history were also excluded.The criteria of the Declaration of Helsinki  and the Manual joint testing was performed for subgroup stratification into "no pain," "local pain," and "referred pain to the head" groups, using a protocol based on the study by Luedtke and May . Gentle For the stratification, the pain responses to all palpation points were combined. However, if several measurable variables are combined into one value, it is assumed that they measure the same hypothetical or latent construct . In thisFirstly, the hypothesis of unidimensionality of the palpation points of the segments C1 to C3 was tested. Therefore, a factor analysis ) of all six palpation responses was performed based on a Spearman's rank correlation , 19. An Then IRT modelling was used to assess the psychometric properties of the underlying construct and related items. Because of the ordinal response options of the single items  polytomous item response theory (IRT) models were used . First, n = 56) and frequent episodic migraine (n = 15) met the inclusion criteria. Overall, 89% of participants were female, 65% reported headache during examination, and 17% were examined interictally  when compared to the partial credit model) [The rating scale model (RSM) described by Andrich (1978) showed the best model-data fit statistics  . The RSMt model) .After fitting the RSM, item hierarchy was investigated using the boundary characteristic curves (BCC) see Fig. . The BCCFigure In summary the results show that the palpation point C3 can be excluded for subgrouping patients as it does not form one latent construct with the palpation points C1 and C2 and therefore the segments occiput-C2. All palpation points on C1 and C2 are important but C2 has a higher probability to show a painful response in a stratification assessment.The purpose of this secondary analysis was to identify whether C3 should be added to the palpation procedure when assessing patients with migraine and thereby to confirm the latent construct for stratification. Results showed that for the stratification of migraine patients, as suggested by Luedtke and May , the palStratification of migraineurs by manual examination has been described in only one study suggesting an associated cervical component in migraine patients differing across subgroups . The ratNevertheless, work by Carvalho and colleagues showed that subgroups differed with respect to the frequency of migraine attacks . TherefoA strong association of referred pain is frequently reported between V1  and GON. However, referred or radiating pain is reported much less frequently between V1 and the two branches of the trigeminal nerve V2 and V3, although these are nerve branches of the same nerve, but apparently show less convergence to V1 in the TCC than the GON. Clinically, this difference is reflected in the fact that while up to 76% of migraine patients report neck pain, only 2.3%  to 8.9% As early as 1944, it was investigated in healthy subjects how far pain caused by noxious stimuli to the periosteum and muscles from different cervical segments radiates. It was shown that the farther cranially the stimulus was administered, the farther the radiation extended. Stimuli at the level of C2 and C1 reached frontal and orbital regions , 30. TheThe present study did not distinguish between migraine patients and healthy subjects. Therefore, results are only valid for the stratification of (severely affected) migraine patients. The examinations of C3, however, might still be important to be included in the manual examination of the cervical region of migraine patients as it might give additional information.The results of the principal component analysis show that the manual examination of the cervical spine on migraine patients should be focused on the unilateral palpation of C1 and C2. It was confirmed that these palpation points form a robust latent construct for the stratification of migraine patients. The categories no pain, local pain and referred pain to the head can easily be use clinically to distinguish between migraine patients with low, moderate or high cervical dysfunction. With a future uniform procedure for stratification, the subgroups can be further examined regarding pathophysiological and clinical differences.


There is an abundance of literature focusing on morphological and surgical outcomes in women with arthritic and prearthritic hip pain. However, no studies have evaluated conservative treatment outcomes, such as physical therapy (PT) and injections, in women with prearthritic or extra-articular hip pain. The purpose of this study is to assess changes in long-term patient-reported outcome measures after nonoperative treatments in women with prearthritic or extra-articular hip pain.Twenty-nine female patients (35–65 years old) who presented to a single provider between December 1, 2012 and September 1, 2017 for prearthritic or extra-articular hip pain (Tonnis 1 or less) and had baseline patient-reported outcome data  available from the institutional hip registry were included. Patients underwent nonoperative treatments for intra-articular or extra-articular hip pain. A follow-up questionnaire was prospectively administered at 3–5 years after the baseline visit.n = 27; 93%) to treat intra-articular or extra-articular hip pain. Targeted PT can be defined as primarily exercise-based therapy focusing on hip and lumbar stability. Twelve patients (41%) received injections; of these, 11 were also treated with PT. Overall, significant improvements in mHHS, HOS-ADL, and iHOT-33 scores were observed . HOS-ADL and iHOT-33 scores improved by a median of 10.3 and 18.0 points, respectively, and were clinically significant. HOS-sport scores also improved but were not statistically significant. There were no differences in patient-reported outcomes between patients who received both PT and injections versus those who received PT, injections, or other treatments.Most patients underwent targeted PT (Nonoperative treatments for prearthritic or extra-articular hip pain in women, specifically PT and/or injections, were associated with sustained improvements in patient-reported outcomes at 3–5 years postbaseline. In recent years, the number of studies investigating the prearthritic hip has increased, specifically observing treatment mechanisms to avoid the development of OA requiring surgical intervention.4–7 Common treatment options include physical therapy (PT), medication, activity modification, patient education, ultrasound/fluoroscopic-guided therapeutic injections, and surgery.8Generalized hip pain is commonly attributed to varying conditions, including osteoarthritis (OA), femoroacetabular impingement (FAI), hip dysplasia, femoral version, tendinitis of the hip joint, degeneration of the labrum, and chondral lesions.9 Joseph et al. observed patients undergoing arthroscopic surgery for FAI and showed that women had poorer self-reported hip function preoperatively. No differences in hip function were found between men and women at 2 years postoperatively.10Prearthritic hip pain that is left untreated has the potential to progress to early OA, highlighting the importance of understanding the mechanisms of injury and pain in these patients. In young adults between 18 and 30 years old, differences in hip morphology between men and women have been observed, such that women have smaller alpha angles and increased anteversion.11 Furthermore, Salvo et al. demonstrated that men and women undergoing hip arthroscopy differed in preoperative hip function, morphology, and self-reported functional deficits. However, men and women did not differ on symptom location, duration, or onset.12 Several studies have supported the finding of sex-dependent differences in hip function, morphology, and patient-reported outcomes in patients receiving hip arthroscopy.14 In patients presenting with symptomatic hip labral tears, Lindner et al. observed sex differences in hip structure, biomechanics, and operative findings.15 Finally, Meghpara et al. reported that both men and women demonstrate improved outcomes and clinical effectiveness at a minimum of 2 years after gluteus medius repair.16In addition, Malviya et al. observed that women reported lower quality of life than men both before and after hip arthroscopy for the treatment of FAI.Although it is clear that the literature has evaluated surgical outcomes for prearthritic hip pain in women and sex-based morphological differences, no studies to date have evaluated long-term outcomes specifically for women with prearthritic hip pain after nonoperative treatments, such as PT and injections. Along the same lines as previously cited surgical studies, certain conservative treatment options may work better for women in comparison with men when presenting with prearthritic or extra-articular hip pain. Studying these specific outcomes as it pertains to female patients is an essential first step to treating patients with the highest standard of specialized care, further improving our treatment options and strategies. Thus, this study aims to assess and report on long-term patient-reported outcomes after nonoperative treatments in women presenting with prearthritic or extra-articular hip pain.This retrospective study with prospective follow-up was approved by the Institutional Review Board (IRB No. 2017-1098), and verbal informed consent was obtained from all patients. The verbal informed consent process was approved by the Institutional Review Board. Female patients (35–65 years old) who presented to a single provider with prearthritic or extra-articular hip pain, were part of the institutional hip registry, had available baseline patient-reported outcome data from the registry, and completed a follow-up at 3–5 years postbaseline visit were included in the study. Exclusion criteria included male patients, ages <35 or >65 years, and arthritic-related hip pain (Tonnis grade: 2+). The age range of 35–65 years old was selected, as it was the nature of the respective group and an efficient way to rule out an indication of OA.17Demographic and treatment data were collected from electronic medical records. The modified Harris Hip Score (mHHS), Hip Outcome Score , and International Hip Outcome Tool-33 (iHOT-33) were administered to patients at their baseline visits, as part of the registry. These outcome measures were also prospectively administered at 3–5 years after the baseline visit, as part of this study. Increases in scores over time represent improvements in outcomes. The minimal clinically important differences (MCIDs) are 8.2, 8.3, 14.5, and 12.1 points for mHHS, HOS ADL, HOS sports, and iHOT-33, respectively.p < 0.05. All analyses were performed with Stata, version 14.2 .This was a convenience sample of patients who were part of an institutional registry and completed the prospective follow-up at 3–5 years after their baseline visits. Continuous variables are reported as medians and interquartile ranges (IQRs), whereas discrete variables are reported as frequencies and percentages. The Wilcoxon rank-sum test was used to compare follow-up outcome scores with baseline. Statistical significance was defined as 2 (IQR: 20.7–26.3). One patient had concurrent knee pain; none of the patients had concurrent back or hamstring pain. The median duration of pain was 6.5 months (IQR: 5.5–13). Diagnoses included gluteal tendinitis or gluteus medius tendinopathy (n = 13), hip impingement (n = 9), psoas tendinitis (n = 9), dysplasia (n = 6), osteitis pubis (n = 1), and right inferior pubic ramus fracture (n = 1).A total of 29 patients with complete data sets were included in the study. The median age at the time of the baseline visit was 49 years (IQR: 43–53), and 28 (97%) patients were of Caucasian race. The median body mass index was 22.1 kg/mn = 27; 93%) that focused on both lumbar and hip stability to treat their prearthritic or extra-articular hip pain. Patients attended 1–2 sessions of PT per week for a duration of 6 weeks. For targeted PT, therapists were instructed to focus on exercise-based therapy of the hip, specifically focusing on balance training, biomechanics, hip adductor strengthening, low-back strengthening, glut/hip abductor strengthening, posture, body mechanics, trunk stabilization, spine stabilization, core strengthening, and small muscle control. PT was provided in a stepwise progression with functional goals. The standardized prescription used for PT is shown in Most patients underwent targeted PT , acupuncture, icing, and yoga.Twelve patients (41%) received injections; 2 (16.7%) received hamstring platelet-rich plasma (PRP) injections, 7 (58.3%) received ultrasound-guided corticosteroid injections of the hip joint, 2 (16.7%) received ultrasound-guided trochanteric bursa corticosteroid injections, and 1 (8.3%) received a facet joint injection. Of these 12 patients who received injections, 11 were also treated with PT. Other reported treatments included medications . HOS ADL and iHOT-33 scores improved by a median of 10.3 and 18.0 points, respectively, thus meeting MCID criteria for both outcome measures. HOS sport scores also improved, although statistical significance was not met. One patient underwent hip surgery during the 3- to 5-year follow-up period; all outcomes worsened for this patient. A closer look at the treatments revealed no differences in any of the patient-reported outcomes between patients who received both PT and injections versus those who received PT, injections, or other treatments alone  of patients received PT, and 41% (n = 12) received injections. Eleven of the 12 patients who received injections also underwent PT. There were no differences in patient-reported outcomes between patients who received both PT and injections versus those who only received PT, injections, or other treatments.In this cohort of 29 female patients, there were significant improvements in mHHS, HOS ADL, and iHOT-33 scores at 3–5 years after the baseline visit. Improvements in HOS ADL and iHOT-33 scores were both clinically and statistically significant. Ninety-three percent  in women with FAI.21 Nakahara et al. found gender differences in joint orientation and shape around the joint, including the acetabular rim and the femoral neck, ultimately leading to differences in range of motion until bony impingement.20 Decreased center edge angle and increased acetabular inclination angles in females suggest a tendency toward dysplasia. Furthermore, Beaule et al. and Ganz et al. observed an increased anterior over-coverage of the acetabular rim in females, suggesting that pincer-type FAI is more common in females.23 Based on the poor surgical outcomes and anatomical differences in women presenting with hip pain, a further analysis of nonoperative treatments for prearthritic hip and pelvic pain is essential.It has been established in the literature that females present with greater acetabular anteversion, acetabular inclination, femoral neck anteversion, and decreased lateral center edge angle.Predicated by the poor surgical outcomes in women, nonoperative treatments should be the first step in treating prearthritic or extra-articular hip pain, taking into account all anatomical features and sex differences in the presenting pathology. Our results demonstrate that nonoperative treatments, including targeted PT and injections such as corticosteroids and PRP, were associated with improved patient-reported outcomes at the 3- to 5-year mark after the baseline visit. Based on our results, future studies should investigate higher-powered studies observing the direct relationship between improvements in patient outcomes and nonoperative treatments. By doing so, physicians can gain a better understanding of the efficacy of nonoperative treatments in the prearthritic hip pain population, avoiding unnecessary surgical interventions.n = 29). However, we believe that our findings provide necessary insight into the long-term outcomes of nonoperative treatments in women with prearthritic or extra-articular hip pain, which are lacking in the literature. As this was a retrospective study with prospective follow-up, we did not have a control group for comparisons. In addition, most patients were between the ages of 43 and 53 years, and were predominantly of Caucasian race, thus limiting the generalizability of our results.This study is not without limitations. The sample size was relatively small (In addition, specific data on nonoperative treatments, such as specific PT exercises and duration of PT, were not compared between participants. Patients were asked to provide as much information as possible regarding treatments they had received during the follow-up period; however, some treatments may have been missed. Finally, this study investigated a cohort of patients who received treatments with prearthritic or extra-articular hip pathologies to gain information on overall long-term outcomes after these treatments; however, future studies should focus on outcomes after specific treatments for specific hip pathologies.In this cohort of female patients with prearthritic or extra-articular hip pain, nonoperative treatments, such as PT and injections, were associated with improved function and disability outcomes at 3–5 years postbaseline. Future higher-powered studies should investigate the direct relationship between conservative treatments and patient-reported outcomes in women with prearthritic or extra-articular hip pain. Furthermore, more targeted studies should investigate sex-related differences in patient-reported outcomes based on the conservative treatments received, ultimately determining which treatment options work best for specific patient groupings.


Background: Back pain is a rare initial presentation of gastric cancer. Isolated back pain with red flags in middle-aged patients might indicate multiple myeloma. However, it is rarely present in advanced gastric adenocarcinoma; hence, data are limited to case reports only. For a timely diagnosis of the underlying malignancy, endoscopy should be considered if the initial workup for this backache is unrevealing.Case Presentation: We present a 34-year-old previously healthy gentleman with severe unremitting backache. He was ultimately diagnosed with gastric adenocarcinoma stage IV and received palliative treatment. The manuscript also reviewed relevant literature.Conclusion: In rare cases, gastric malignancy can initially present as back pain with lytic bone lesions, mimicking multiple myeloma. Endoscopy early in the course of investigations may help reduce associated morbidities. Further, more extensive studies are required to understand better the clinical characteristics, demographics, and management of such patients. Majority of cases (approximately 75%) present with constitutional symptoms such as weight loss, appetite loss, and fatigue accompanied by specific symptoms such as hematemesis, melena, abdominal pain, vomiting, and fullness. GC can manifest atypically, leading to a diagnostic challenge and potential delay in timely diagnosis and management. Back pain accompanied by lytic lesions in the vertebrae is usually characteristic of multiple myeloma (MM). The incidence of bone metastasis from GC is estimated to be 13.4% in autopsy specimens. However, bone metastasis is higher in advanced stages than in early presentation. Back pain is sporadic as an initial complaint in patients diagnosed with GC, with a few cases reported in the literature. Identifying the etiology underlying such back pain is important. Differentiating the type of underlying malignancy based on the characteristics of the back pain, as in GC and MM secondary to bone metastasis causing a similar type of pain, is usually difficult. Signet cell carcinoma appears to be the most common histopathological type associated with back pain as an initial presentation in patients with GC. This report presents a similar case and reviews previously published cases to highlight this rare presentation of GC. In this case, the patient was male and presented with back pain, revealing lytic vertebral lesions that mimicked the common presentation of MM, ultimately revealing an advanced GC.Gastric cancer (GC) is a common malignancy. With more than 780,000 deaths annually, GC is the third deadliest malignancy among men.A 34-year-old Bangladeshi patient presented with severe back pain for 2 weeks. The low back pain was severe, which kept him up at night. He described it as the worst pain he had ever felt, characterizing it as a dull pain with 10/10 intensity. His pain was initially intermittent for the first few days but later became incessant, worsening with slight movement. The pain was non-radiating and did not tend to shift to any other parts of the body. However, it was associated with a different sharp, diffuse abdominal pain, which was persistent. He had two episodes of non-bilious, non-bloody vomiting the day before admission. He had no history of fever, weight loss, night sweats, melena, hematemesis, smoking, or alcohol use. He did not have any medical problems and was not taking any medications.The patient was afebrile (36.6°C) and had normal hemodynamic parameters . During the physical examination, back tenderness, abdominal tenderness, organomegaly, or palpable lymph nodes were not noted; only pallor was notable. Initial laboratory findings revealed microcytic anemia, thrombocytopenia, altered liver function tests with an obstructive pattern, and hyponatremia . FurtherHelicobacter pylori (H. Pylori)  . A diagnH. pylori eradication treatment.A multidisciplinary team meeting was conducted, involving the internal medicine team, oncology team, hematology team, radiotherapist, histopathologist, gastroenterologist, and palliative team. Palliative care was decided due to the advanced stage of the disease. The patient received analgesics (morphine and gabapentin) for his worsening back pain, packed red blood cell transfusion, folic acid, and iron replacement. He also received the Pyloric obstruction was stented. The patient was also treated with palliative radiotherapy to the lumbosacral spine (20 Gy in four fractions) and dexamethasone 4 mg intravenously twice daily to address his back pain and autoimmune hemolytic anemia, which was considered secondary to his malignancy. He completed the planned four radiotherapy sessions, and his back pain improved partially . The patient traveled back to his home country for further treatment. Although abdominal pain presents in >60% of patients with GC, it is neither sensitive nor specific to GC. Less common symptoms present in 20%–35% include nausea, anorexia, dysphagia, and melena. We used PubMed, Scopus, and Google Scholar to conduct a systematic literature search using relevant search terms. We identified 610 articles, of which 10 were reviewed in detail after careful screening. We used the following MeSh terms to identify relevant articles from the databases: “stomach neoplasms” OR (“stomach” AND “neoplasms”) OR (“gastric” AND “cancer”) OR “gastric cancer” OR “adenocarcinoma” OR “adenocarcinomas” AND “back pain” OR (“back” AND “pain”) OR “vertebra.”*.”GC is commonly asymptomatic and often presents in the advanced stages. Most commonly, GC presents as persistent abdominal pain associated with weight loss.Among the 10 patients discussed in this report , 6 were men, and 4 were women. The average age was 51.2  years. More than 50% of the patients presented with lower back pain, whereas the rest had upper and mid back pain. Moreover, 30% of the patients reported anorexia and weight loss in addition to back pain. Fatigue and fever were concomitant symptoms in two patients. Results are summarized in Additionally, abdominal pain, bloating, heartburn, nausea, and vomiting were reported in 10% of the patients. None of the patients had hematemesis or melena. Most patients had no prior illness, except for one patient with hypertension and two patients with diabetes. Smoking was reported in 30% of the patients. Most of these patients were initially screened with X-ray imaging, but they all had further imaging with CT and MRI. Lytic and sclerotic lesions were equally predominant in radiological studies. Two patients had collapsed vertebrae. The most involved vertebrae were the thoracic and lumbar vertebrae. Only one patient had cervical spine involvement.Interestingly, four patients were diagnosed by bone biopsy or bone scan, which warranted the gastric biopsy for definitive diagnosis. Gastric tumors were preponderant in the antrum. All patients had gastric adenocarcinoma, with 60% showing signet-ring cell features. Half of the patients were started on active treatment, whereas the rest received palliative care. The cancer progressed in 6 of the 10 patients, and they were deceased by the time their cases were reported. Of these, weight loss, anorexia, dysphagia, and melena are considered alarm symptoms because they correlate with a worse prognosis. Stephens et al. followed 300 consecutive patients with gastric adenocarcinoma. They concluded that the presence of alarm symptoms correlate with a more advanced tumor stage and a more proximal location of the neoplasm. Another report of 4000 patients demonstrated that dyspepsia associated with only one of the alarm symptoms has a significant 26% reduction in 5-year survival rate compared with patients without alarm symptoms.While early satiety is a known symptom of GC, it presents in only 17% of patients and is often associated with later stages of the disease.Patients with GC with a long history of dyspepsia without associated alarm symptoms have less advanced stage and a better prognosis than patients with a short history of abdominal pain and alarm symptoms. Hussain et al. reported a case where GC with early bone metastasis was complicated by bone marrow infiltration, causing anemia and disseminated intravascular coagulation. The coagulopathy also resulted in spinal hemorrhage and spinal cord compression. Sandilya et al. reported a patient with back pain associated with acute kidney injury who was found to have metastatic GC. However, the back pain was caused by peritoneal carcinomatosis and urinary bladder wall metastasis. Future studies are required to elucidate the behavior of GC metastasis and recommend specific treatment modalities to target such conditions.Only a few cases of presentation with back pain from bone metastasis in GC has been reported, as presented above. It is essential to highlight this type of presentation, as it can mislead and direct the diagnostic search toward other diseases, which more commonly present in adulthood and early old age with back pain and lytic lesions in the vertebral column, especially MM. The median survival ranges from 3 to 5 months with the best supportive care. In GC with bone metastasis, chemotherapy or radiation treatment reduce pain. Hironaka et al. reported the effectiveness of sequential methotrexate and 5-fluorouracil for GC with bone metastasis. In the 2008 S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced GC trial, Koizumi et al. reported an increase in the median overall survival for S-1/cisplatin therapy (13 months) compared with S-1 alone (11 months). According to Yoshikawa and Kitaoka, radiation therapy was effective for the palliation of bone pain in 23 patients with GC associated with bone metastasis.The treatment goals of metastatic GC are prolongation of survival, improvement of the quality of life, and symptom palliation.Back pain is a rare initial presentation of GC without accompanying signs or symptoms and appears to carry a poor prognosis. Clinicians must consider gastric malignancy while working up these patients for a diagnosis. Endoscopy should be a part of investigations with patients whose initial workup does not identify a cause. Further, more extensive studies are warranted to understand better the clinical characteristics, demographics, and management of such patients.None.This study was not funded.None of the authors have any conflict of interest to disclose.This work is original, has not been, and is not under consideration for publication in any other journal. All authors have reviewed and approved the final version of the manuscript. The study was approved by the Medical Research Centre (MRC) Qatar (MRC-04-21-912).Written informed consent for submitting this case report was provided by the patientNot applicable.FA: methodology, literature review, data collection and interpretation, manuscript writing, and finalization.MB, AA, MF, and GK: literature review, data collection and interpretation, and relevant manuscript writing.AB: provision of radiological images and relevant manuscript writing.OE: provision of histopathological images and relevant manuscript writing.ZY and AJ: supervision, literature review, and editing of the manuscript.


They also had a lower gray matter volume (GMV) in the bilateral insula, left angular gyrus, precuneus, left inferior temporal gyrus, and left postcentral gyrus . Similarly, decreased voxel-mirrored homotopic connectivity was observed in the bilateral insula, posterior cingulate cortex, middle frontal gyrus, and postcentral gyrus in the adenomyosis patient group . Regional homogeneity showed significant differences mainly in the bilateral cerebellum, left inferior frontal gyrus, medial prefrontal cortex, and posterior cingulate gyrus. Correlation analysis showed that the degree of depression in patients with adenomyosis was negatively correlated with the GMV of the left angular gyrus. The results show that these patients exhibited changes in multiple brain regions associated with pain as well as emotion perception and processing.The absence of clinically objective methods to evaluate adenomyosis-associated pain and the poor understanding of its pathophysiology lead to treatment limitations. We conducted a resting-state functional magnetic resonance imaging study with 49 patients with pain-related adenomyosis and 30 pain-free controls to investigate brain morphological alterations and regional dysfunctions in patients with pain-related adenomyosis. These patients had significantly higher scores for anxiety and depression than the control group ( Adenomyosis (AM), characterized by the invasion of endometrial mucosa within the myometrium, is a common, benign, and chronic gynecological disorder with an indeterminate etiology ,2. AM syInterestingly, a strong association was found between AM and endometriosis (DIE), and there were clinical and pathologic similarities and distinctions between the two conditions, especially dysmenorrhea and chronic pelvic pain . Our preResting-state functional magnetic resonance imaging (fMRI) is based on blood-oxygenation-level-dependent (BOLD) spontaneous activity . AnalytiThis study aims to investigate brain morphological and functional changes in AM patients with pain, and the correlation between the changes in the brain and the degree of anxiety and depression. Ultimately, we aimed to investigate the neural mechanism of pain in patients with AM and provide a more objective pattern of pain assessment for AM.This study was registered on chictr.org.cn  and approved by the Medical Ethics Committee of the Qilu Hospital of Shandong University; all of the participants signed informed consent forms. The participants were enrolled in the obstetrics and gynecology ward of the Qilu Hospital of Shandong University between May 2020 and April 2021.This study included 50 right-handed patients with AM. The inclusion criteria for AM patients were as follows: (1) age between 20 and 50 years; (2) gynecological ultrasound findings suggesting AM according to the Morphological Uterus Sonographic Assessment (MUSA); (3) numeric pain rating scale score ≥4 and dysmenorrhea or chronic pelvic pain of at least 6 months duration; and (4) requiring surgery. In addition, the AM diagnosis confirmed only by postoperative pathology and no ovarian endometriosis cysts or deep endometriosis were found during surgical exploration. The exclusion criteria were as follows: (1) pregnancy or lactation; (2) presence of other chronic pain conditions , includiAll of the participants were evaluated by a gynecologist and underwent conventional MRI scans to exclude anatomical brain abnormalities. Demographic data and questionnaires were collected, and fMRI was performed pre-operatively. One patient with AM was excluded because of an image acquisition error. The final imaging and correlation analyses included 49 patients with AM and 30 controls.Before the study, all of the participants were informed of the study methods, procedures, objectives, and potential risks. Demographic information, including age, body mass index (BMI), menstrual status, and childbearing history, was obtained through an interview and clinical examination by a professional gynecologist. Additionally, the clinical data, such as hemoglobin (HGB) level and uterine volume, were collected before the surgery.The numeric rating scale (NRS), with scores ranging from 0 to 10, was used to assess the mean pain intensity in the past 6 months, including dysmenorrhea, dyspareunia, dyschezia, and non-menstrual pelvic pain ,24. All MR images were acquired using a Siemens Verio 3.0 Tesla MR scanner . To minimize head movement, tight and comfortable foam padding was used, and earplugs were also provided to all of the participants to muffle the scanner noise. Resting-state fMRI data were obtained using a gradient-echo single-shot echo planar imaging sequence with the determined imaging parameters . During http://www.fil.ion.ucl.ac.uk/spm (accessed on 1 August 2019) and Data Processing and Analysis (DPABI) for (Resting-State) Brain Imaging [The fMRI data were preprocessed using Statistical Parametric Mapping , which were corrected using the AlphaSim program in REST plus software.The Statistical Package for the Social Sciences  was used for the statistical analyses, and the level of significance was set at p < 0.05, Bonferroni correction). Pearson’s correlation was applied to normally distributed data.Correlation analyses were applied to detect the associations between the clinical characteristics  and mean GMV and altered function in all of the participants within each region of interest (p > 0.05). There was no significant difference between the AM and control groups in terms of age, BMI, menstrual status, and childbearing history (p > 0.05). In contrast, the proportion of menorrhagia in the AM group was higher than in the control group (p = 0.001). In addition, the AM group had lower HGB levels and greater uterine volume than those of the control group (p < 0.001).The demographic information and clinical characteristics of all of the participants are listed in p < 0.001). As expected, there were significantly higher SAS and SDS scores in the AM group than in the control group (p < 0.05).The pain intensity of the AM group was higher than that of the pain-free group  than that of the control group. No brain regions showed greater GMV in patients with AM than in pain-free participants. Furthermore, both the SAS and SDS scores were negatively correlated with the GMV of the left angular gyrus and left postcentral gyrus   . The SAS 0.0001) c,g. TherOur study suggests that the patients with pain-related AM had a significantly lower GMV and decreased functional activities in several brain regions associated with pain perception and emotion regulation. The results were verified by different analyses, including VBM, VMHC, and ReHo. All of the participants’ degrees of pains correlated with several brain regions. Additionally, dysfunction in the left angular gyrus was significantly correlated with the SDS scores in the patients with pain-related AM.The AM patients with dysmenorrhea and chronic pelvic pain are more sensitive to experimental pain outside of menstruation than the pain-free women, a phenomenon known as hyperalgesia ,30. StudHere, we used resting-state fMRI to explore alterations in the brain regions, and similar results were obtained by different methods. First, our study revealed lower GMV in patients with AM in the bilateral insula, left angular gyrus, precuneus, left inferior temporal gyrus, and left postcentral gyrus. Further, decreased VMHC was observed in the bilateral insula and postcentral gyrus in the patient group. As a cortical convergence region, the insula participates in various processes, from somatic perception to emotional conflict, receiving information directly from the spinothalamic tract ,33. NeurBased on the resting-state fMRI, we analyzed the different functions between the patients with pain-related AM and the pain-free controls in VMHC and ReHo. The medial prefrontal cortex (MPFC) is known as a key region of pain processing, which is also an important component of the DMN. Here, the decreased ReHo values in MPFC were found in the pain group, consistent with previous findings in patients with chronic pain . A studyThe studies have demonstrated structural and functional abnormalities of the cingulate gyrus in human and rat models of pelvic pain caused by primary dysmenorrhea ,40. UsinOur study had some limitations. First, the sample size was not sufficiently large, and we did not perform a power analysis; more convincing results may be obtained by increasing the number of participants. Second, more studies are needed to verify the reliability and repeatability of this study. Thirdly, in the control group, adenomyosis was excluded by gynecologic ultrasound but not pathology. Finally, longitudinal studies are needed to investigate whether the changes in the brain regions are caused by persistent pain or changes leading to hyperalgesia in patients with AM.We preliminarily demonstrated that pain leads to morphological and functional changes in brain regions related to pain in patients with AM. This could offer novel insight into understanding the neural mechanism of pain in patients with AM and be helpful for the objective assessment and individualized treatment of patients with pain-related AM.