Lumbar disc herniation (LDH) is one of the most common conditions associated with functional disability, affecting patients’ quality of life (QOL). Disability can be affected by cognitive factors, such as pain catastrophizing. Similarly, unfulfilled basic psychological needs  are associated with biases in pain perception and QOL. Using the fear-avoidance model and the self-determination theory, this study investigates: (1) the separate contribution of pain-related variables and basic psychological needs satisfaction in predicting QOL in patients proposed for LDH surgery; (2) pre- and post-surgical differences in pain catastrophizing and basic psychological needs satisfaction.age = 46.10, SDage = 11.40) to identify predictors of QOL. Second, we performed paired t-tests on 55 patients to investigate pre- and post-surgical differences in pain catastrophizing and basic psychological needs satisfaction.First, we used hierarchical regression on 193 patients  = 6.07, This research confirms the importance of pain perception and pain catastrophizing for LDH patients’ QOL and broadens the applicability of the self-determination theory for spinal patients. The mosAll these manifestations lead to functional disability or impairments in accomplishing basic activities of daily living  and instrumental activities of daily living  to examine the contribution of pain-related variables and BPN satisfaction in predicting QOL in adult patients proposed for LDH surgery; (2) to investigate the pre-surgical and post-surgical differences in pain catastrophizing and BPN satisfaction in patients undergoing LDH surgery. We expect patients to have lower levels of pain catastrophizing after surgery, in line with previous studies. Also, exploratory, we anticipate that BPN satisfaction will significantly increase after surgery when patients have good prospects of resuming their daily activities shortly.2.2.1.age = 11.40. The gender distribution was relatively balanced, with 102 females (53%) and 85 males (44%). Six participants did not disclose their gender. Most participants were employed. A subsample of 55 patients was also assessed after surgery with pain and BPN satisfaction measures. They had similar gender characteristics as the main sample: 28 females (51%) and 27 males (49.%), with Mage = 51.29 (SDage = 1.33). We excluded patients who met one or more of the following criteria: (1) had major surgical interventions in the past, (2) had a terminal illness, (3) had other chronic pain conditions, (3) had a psychiatric diagnosis, (4) had a disability certificate.This study was conducted on a sample of patients with intense back pain. The sample consisted of 193 adult patients with LDH, hospitalized, and proposed for surgical intervention at the “Bagdasar-Arseni” Emergency Hospital in Bucharest, Romania, before the COVID-19 pandemic. Using a cross-sectional design, the participants were assessed before surgery and had a mean age of 46.10, with SD2.2.After hospital admission, the patients with intense back pain were asked to participate in this study. Each patient eligible for inclusion was informed about the study’s aims and gave informed consent for participation. The study followed the principles of the Declaration of Helsinki. All the participants presented pain related to their undergoing clinical condition; therefore, they were fully assisted by a researcher specialized in clinical psychology as they completed the measures. A subsample of 55 patients also completed pain catastrophizing and BPN satisfaction measures after LHD surgery. The process can be visualized in the 2.3.2.3.1.I have no problems…) to 5 (I am unable to…) in each dimension. For further analysis, we used the sum of scores for the three dimensions. Bigger scores indicated lower QOL. The internal consistency for the three subscales of QOL was acceptable (Cronbach’s α = 0.76).Quality of life perception was assessed with EQ-5D-5 L , which is designed as a general measure for health-related quality of life. The scale has five dimensions, but we used only the three dimensions that assess functional disability in the following areas: mobility, self-care, daily life activities. We chose these dimensions as they are the most relevant when it comes to functional impairment in patients with intense lower back pain . The ite2.3.2.Pain intensity was assessed using a numeric pain rating scale NRS; . We eval2.3.3.α = 0.93).Pain catastrophizing was investigated with The Pain Catastrophizing Scale PCS;  a measur2.3.4.α = 0.83).Basic psychological needs satisfaction was assessed using the Basic Psychological Needs Satisfaction Scale , a 9 ite2.4.p < 0.05 being considered the minimum acceptable cutoff. We used hierarchical linear regression to investigate the contribution of the chosen predictors for explaining QOL. The main assumptions of hierarchical regression were met. In the first step, we introduced the demographical variables (age and gender) as control variables. In the following steps, we included medium pain level, pain catastrophizing, maximum pain level and BPN satisfaction, in the order of their descending correlation with QOL. The components of BPN satisfaction were not introduced separately in the regression equations due to concerns of multicollinearity. Finally, we reported unstandardized and standardized B coefficients and standard error for B, confidence intervals, and value of ps. For investigating the pre-surgical and post-surgical differences in pain catastrophizing and BPN satisfaction, we used the paired samples t-test and reported the appropriate indicators .We analyzed the data using Jamovi software version 1.19. First, means, standard deviations, and normality indicators were reported, along with the Pearson correlations for all the variables in the study. To test the normality of the distribution, we used the skewness and kurtosis indicators, with acceptable values ranging from −1.96 to +1.96 . Next, w3.3.1.Participants with higher medium and maximum pain levels, more intense pain catastrophizing thoughts, and older age reported lower QOL, as expected. There was no significant correlation between BPN satisfaction and pain levels. For details, please consult N = 138) and the subsample assessed also post-surgically (N = 55), we found that the groups were similar in terms of medium , maximum  pain levels and catastrophizing . At the same time, the following differences were observed: the subsample evaluated also post-surgically was older compared to the former  and reported lower BPN satisfaction levels .In terms of comparisons between patients assessed only pre-surgically (3.2.p < 0.001) and explains 27% of QOL’s variance.For the study’s first aim, a hierarchical linear regression analysis was conducted to evaluate the prediction of quality of life from pain levels, pain catastrophizing, and each BPN component. The predictors were entered in separate steps, in the order of their descending correlations with the criterion. Additionally, the contribution of age and gender was isolated in the first step of the regression. As presented in F  = 7.53, p < 0.001, R2 = 0.07]. In Step 2, we added the medium pain level, which upgraded the model’s prediction power to 22% . Medium pain alone explains 14% of QOL’s variance. Pain catastrophizing, the predictor introduced in Step 3, also brings additional explicative value . Maximum pain level included in Step 4 does not bring additional explicative value over the other variables . In contrast, BPN satisfaction inserted in Step 5 brings a small but significant contribution over the other variables . All these results are summarized in Step 1 is significant, which means that the control variables significantly contribute to the model  and associated subscales did not change significantly after surgery. This result is probably due to the fact that data were collected shortly after surgery before patients left the hospital and resumed their activities, and BPN satisfaction is a concept that reflects long-term functioning. All the results are detailed in As expected, pain catastrophizing decreased significantly after surgery, with a large effect size [t (54) = 6.07, 4.This study aimed to investigate: (1) the separate contribution of pain-related variables and BPN satisfaction in predicting QOL of patients with LDH before surgery; (2) the differences in pain catastrophizing and BPN satisfaction before and after LDH surgery. Understanding these interactions can extend the applications of the SDT theory and consolidate the contribution of biopsychosocial factors in LDH patients’ QOL.The regression analyses showed that medium pain level, pain catastrophizing, BPN satisfaction and age were significant predictors of QOL in the presumed direction. The results reinforce the contribution of the Fear Avoidance Model  and the Pain catastrophizing, one of the most prevalent psychological risk factors for pain and disability  also preAge predicted QOL and this finding is in line with previous work showing that functional disability levels increase as we grow old due to the natural degenerative processes in the human body and different risk factors  . The degRegarding the second aim of this study, the results showed that patients’ pain catastrophizing scores significantly decreased after surgery, as presumed, but the BPN satisfaction levels did not increase significantly. As stated previously, before their discharge, the patients were still in post-operative recovery and probably could not perceive any differences regarding their autonomy, self-competence, or their social connections with others. The participants’ age could have also impacted this result, since their mean age was 51 years and recovery is usually slower . TherefoAs such, the current study assists in this direction by highlighting the contribution of pain-related variables and BPN satisfaction to functional disability aspects of QOL, a major concern for patients with LDH. Nevertheless, it is necessary to discuss the study’s main limitations, especially from a methodological point of view. The cross-sectional design used in the hierarchical regression gives insight on the data at a single point in time, providing no information regarding temporal changes in pain-related variables and QOL. The findings can not be generalized due to the convenience sampling method. This type of sampling method introduces biases in data collection, such as self-selection and sampling bias. However, most findings were in line with existing evidence.http://doi.org/10.17632/7tgc2bmkw3.1.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: The studies involving human participants were reviewed and approved by the Ethical Council of Bagdasar-Arseni Emergency Hospital. The patients/participants provided their written informed consent to participate in this study.DI and EA contributed to the conception and design of the study. DI, EA, and FB contributed to its implementation. CI performed the statistical analysis. DI and CI wrote the first draft of the manuscript. EA and FB reviewed the manuscript. All authors read and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Intra-articular (IA) ultrasound-guided hip injections are currently considered a cornerstone of the conservative management of symptomatic hip osteoarthritis (HOA), although their effect on clinical outcomes has not been fully elucidated.The purpose of this study is to investigate the effectiveness of ultrasound-guided IA hip injections of hyaluronic acid (HA) with or without corticosteroids (CS) on pain relief and functional improvement in patients with HOA. In total, 167 patients with HOA were assessed at baseline (T0) and 12 months after injection (T1) using the VAS and GLFS scores. The sample consisted mainly of female subjects (58.1%), presenting an average age of 70.6 ± 12.2 years and grade 3 HOA (63.9%) according to the Kellgren–Lawrence classification. Most of the patients (76.2%) underwent unilateral hip injection with a combination of medium-high molecular weight HA (1500–2000 kDa) and CS. At T1, lower use of anti-inflammatory drugs, an increase in the consumption of chondroprotectors, and an overall reduction of instrumental physical therapies and therapeutic exercise were recorded. In addition, a statistically significant intragroup and between-group decrease observed at T1 for both the VAS and GLFS. Study results suggested that intra-articular hip injections with HA alone and with CS could represent a useful therapeutic tool for pain reduction and functional improvement for patients with hip osteoarthritis. Osteoarthritis (OA) is the most common joint disease, affecting about 400 million people worldwide . The impThe significant social impact of OA seriously and progressively invalidates a patient’s quality of life and determines a substantial rise in public health costs as a consequence of impaired work productivity and early retirement , represeOsteoarthritis typically affects the weight-bearing joints, with the hip being the second most frequently involved large joint after the knee .Hip osteoarthritis (HOA) is one of the most frequent osteoarticular conditions affecting the elderly population . RadiogrNowadays, the prevalence of total hip arthroplasty is increasing . This meThe conservative management of HOA is based on a combination of nonpharmacological and pharmacological modalities ,17. AmonThe IA administration of drugs in the hip joint is increasingly considered a safe and effective therapeutic tool to reduce pain and improve function in hip osteoarthritis , with a Intra-articular injections have become commonly recommended in the management of large joint osteoarthritis ,17. The Different medications can be injected into the hip joint with different levels of evidence-based efficacy, depending on whether they intervene more in the control of inflammation, pain, or mechanical function . The twoCorticosteroids have been shown to be effective in decreasing pain in symptomatic hip osteoarthritis . Intra-aMoreover, the latest available guidelines issued by the OARSI in 2019 provided no recommendation for IA steroid administration in the hip, showing a certain distrust towards pharmacologic interventions in hip OA .The infiltration strategy with CS is often distanced because of important risk factors, such as local infection and soft tissue irritation at the site of injection, the exacerbation of pain, septic arthritis, and chondrotoxicity .Hyaluronic acid is the most used substance in intra-articular infiltrations of the hip or knee and guarantees visco-integration, which seems to have both mechanical and biological effects by restoring the visco-elasticity of the synovial fluid and the lubrication of the joints . AnotherSpecifically, with regard to HA, in the last two decades, viscosupplementation has become popular in clinical practice because of its notable ability to reduce pain, improve function, and possibly delay definitive arthroplasty . AlthougAt best, it has shown a promising effect in moderate-grade hip OA, as shown by Pogliacomi et al. , who repIn the literature, there are currently no studies about the intra-articular administration of the association of HA and CS in the hip joint, with the exception of the study by De Rezende et al. , which sThe aim of this retrospective observational real-life study is to investigate the long-term effectiveness of ultrasound-guided intra-articular hip injections of hyaluronic acid, alone and in association with corticosteroids, for pain relief and functional improvement in patients with hip osteoarthritis.The study was conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards (Protocol number 0039224/21 of 8 November 2021).This retrospective observational study analyzes the data obtained from the medical records of patients with moderate hip osteoarthritis treated with ultrasound-guided hip injections with hyaluronic acid and corticosteroids, alone or in combination, from January 2020 to December 2022, and access was obtained to the outpatient clinics of the Inpatient and Rehabilitation Services Department of the University Polyclinic Foundation Agostino Gemelli of Rome.Informed consent was obtained from all the subjects involved in the study. The participants could withdraw their consent to participate at any time without any consequences.The inclusion criteria were as follows: OA grade > 2 on the Kellgren–Lawrence scale , Mini MeThe exclusion criteria were as follows: age < 18 years, patients with hip prostheses on the affected limb, MMSE < 23, signs of joint infection, severe inflammation, skin disorders or infection at the injection site.The patients were evaluated at baseline before the infiltration treatment (T0) and after 12 months (T1) by telephone interview. Personal and clinical information , pharmacological therapies in progress, ongoing anti-inflammatory and pain-relieving therapies, and rehabilitative treatments in progress related to hip osteoarthritis were collected.Pain assessment was performed using the VAS scale, and the degree of disability and the level of autonomy were measured using the Geriatric Locomotive Function Scale (GLFS-5)  at baselt test for the independent variables and the X2 test for the categorical variables. The assumed confidence level was 95% and the significance was considered for p ≤ 0.05.The statistical analysis was performed using a data processing computer system . For the ordinal and nominal data, descriptive data are reported. For the continuous-interval data, the mean and standard deviation are reported. The comparison between the data was performed using the student’s With regard to the molecular characteristics of hyaluronic acid, a medium-high molecular weight (1500–2000 kDa) was used for most of the patients (96%), while 4% of the patients were treated with low molecular weight hyaluronic acid (620–1200 kDa).In 76.2% of the patients, hyaluronic acid was injected in combination with a corticosteroid (methylprednisolone acetate 40 mg/L mL), while in 23.8% of the patients, only hyaluronic acid was used. The majority of patients (63.9%) had grade 3 hip osteoarthritis according to Kellgren–Lawrence radiological grading , while 0With regard to rehabilitative intervention, the data showed a reduction in the patients who did not perform therapeutic exercise, from 87.3% at T0 to 37.5% at T1, and a parallel increase in the subjects who had already been prescribed a motor rehabilitation program, from 12.7% at T0 to 62.5% at T1. Also, an overall lower use of instrumental physical therapies was detected at T1, with a slight decrease in the percentage of patients who did not perform physical therapies, from 96% at T0 to 87% at T1, and an increase in the patients who performed them, from 4% at T0 to 12.3% at T1.Finally, the percentage of patients who had not undergone hip arthroplasty was 99% at T0, with a reduction to 77.4% at T1. The percentage of patients who were operated on was zero at the baseline, with an increase of up to 20.2% after 12 months. The percentage of patients on the surgical waiting list went from 1% at T0 to 2.4% at T1.The mean changes from the baseline (T0) over 12 months (T1) of the outcome measures are presented in The two groups showed a different sample size, with 127 subjects for the HA + CS Group and 40 subjects for the HA Group at T0 and 79 subjects for the HA + CS Group and 9 subjects for the HA Group at T1.Nowadays, intra-articular injections have become commonly recommended in the management of large joint osteoarthritis, including the hip, which is generally injected under imaging guidance . The demWith regard to the demographic data, our sample consisted mostly of women with a mean age of 70.6 years, which is in line with the epidemiology currently known for hip osteoarthritis with a prevalence of 10–30% in people aged over 60 years , althougRegarding the hip osteoarthritis phenotype possessed at baseline, it was a monolateral osteoarthritis, with moderate pain and mild functional impairment, referring to the VAS and GLFS scales, and of grade 3 according to Kellgren–Lawrence classification, with definite joint space narrowing, moderate osteophyte formation, some sclerosis, and possible deformity of the bone extremities. Radiographic severity has been related to the degree of clinical improvement provided by intra-articular CS injections in the hip ,42. InfaSo, looking at this possible relationship between radiographic damage and pain relief after IA corticosteroid injections in the hip OA, and based on the preliminary encouraging results showing pain and disability reduction with HA and CS association , we deciVarious preparations of HA based on different molecular weights are commercially available, but there is no general consensus on which type is most effective. In our study, a medium-highmolecular weight HA was used, based on the consolidated evidence of the decrease in the concentration and size to 50–33% of HA in an arthritic joint  and follIn addition, regarding the use of high-molecular-weight HA (HMWHA), a recent review with metanalysis revealed that an intra-articular HMWHA injection provided pain relief, functional improvement, and no severe complications on an immediate short-term basis; however, the results do not favor treatment with HMWHA over other treatment methods .From the literature review, the efficacy of hyaluronic acid and cortisone injected separately can be suggested, although evidence from RCTs comparing IA CS injections to viscosupplementation in the hip is quite scarce .In light of the paucity of available data regarding the association of intra-articular HA and CS for the hip joint, our observational study has been primarily designed to evaluate the possible combination of the well-known short-term efficacy of CS with the supposed long-term efficacy of HA in order to design a possible injective treatment protocol for symptomatic HOA in terms of pain reduction and functional improvement.The data on pain and function  showed tIndeed, from a retrospective analysis of the collected data, a statistically significant overall decrease in subjective pain and a functional improvement after one year  can be oThe analysis intragroup and between groups  confirmeNo patients reported immediate or delayed adverse effects, confirming the safety of the ultrasound-guided intra-articular injection when performed according to the standardized technical procedure .A major limitation of our study is the heterogeneity and the different sample sizes of the two injection treatment groups, but this aspect can be justified by the design of the study, which was born as a real-world observational experiment.A second important limitation in the interpretation of the results is the difficulty in determining in what qualitative and quantitative measure the association of hyaluronic acid with cortisone compared to hyaluronic acid alone is more or less effective in improving the clinical and functional outcomes.Intra-articular hip injections have been considered in recent years a cornerstone of the conservative management of symptomatic hip osteoarthritis because they provide significant advantages by inducing a pain decrease, increasing the range of motion, improving functional ability, and reducing the consumption of analgesics. However, further studies are necessarily required to clarify fundamental aspects, such as the HOA-targeted infiltration protocol and the expected therapeutic effect in symptomatic hip OA.The effects of CS in hip OA have been demonstrated in several controlled studies , althougViscosupplementation might improve cartilage biochemistry with chondroprotective effects, even if these aspects have been shown only in vitro and not in human trials ,52,53.Regarding the injective schedule, it will be important to determine the ideal dose of CS, the most biologically suitable hyaluronic acid for association with steroids, but also the recommended rate and maximal number of allowed injections.Regarding the therapeutic effect, targeted trials should also be conducted to establish a precise correlation between the type of injection and the type of hip osteoarthritis. The type of HOA means the radiological grade according to the Kellegren–Lawrence classification and the clinical phenotype based on the prevalence of one of the two main presenting elements of HOA: pain and functional impairment.The growing availability of musculoskeletal US should allow a better and more precise evaluation of the hip environment to create a correlation between ultrasound prognostic elements (for example the degree of synovitis or cartilage thickness) and the corresponding infiltrative protocol.The intrarticular administration of the association of hyaluronic acid and corticosteroids into the hip joint performed under ultrasound guidance could be a useful and safe instrument to reduce pain and improve function in symptomatic HOA in the longterm.However, there is a need for more rigorously designed studies with a larger sample size to further define the evidence-based best practice for intra-articular treatment with the association of hyaluronic acid and corticosteroids for patients with hip osteoarthrosis, which is a subject that is still very much under debate.


A higher percentage of patients in Group 3 received intraoperative sufentanil  and additional techniques for postoperative pain control . Intraoperative hypotension (MAP < 65 mmHg) lasting more than 5 min was more frequent in patients receiving spinal anesthesia, especially with local anesthetics , with the resulting increased need for vasopressors. Recovery-room discharge criteria were met earlier in the spinal anesthesia groups than in the general anesthesia group . No differences were noted in postoperative mobilization or duration of ileus. Conclusions: Intrathecal administration of morphine with or without local anesthetic as a component of blended anesthesia is effective in improving postoperative pain control following laparoscopic or mini-laparotomic hysterectomy, in reducing intraoperative opioid consumption, in decreasing postoperative rescue analgesics consumption and the need for any additional analgesic technique. We recommend managing postoperative pain with a strategy tailored to the patient’s physical status and the type of surgery, preventing and treating side effects of pain treatments.Background: Adequate pain management for abdominal hysterectomy is a key factor to decrease postoperative morbidity, hospital length of stay and chronic pain. General anesthesia is still the most widely used technique for abdominal hysterectomy. The aim of this study was to assess the efficacy and safety of blended anesthesia  compared to balanced general anesthesia in patients undergoing hysterectomy with or without lymphadenectomy for ovarian, endometrial or cervical cancer or for fibromatosis. Methods: We retrospectively collected data from adult ASA 1 to 3 patients scheduled for laparoscopic or mini-laparotomic hysterectomy with or without lymphadenectomy for ovarian, endometrial or cervical cancer or for fibromatosis. Exclusion criteria were age below 18 years, ASA > 3, previous chronic use of analgesics, psychiatric disorders, laparotomic surgery with an incision above the belly button and surgery extended to the upper abdomen for the presence of cancer localizations . The cohort of patients was retrospectively divided into three groups according to the anesthetic management: general anesthesia and spinal with morphine and local anesthetic (Group 1), general anesthesia and spinal with morphine (Group 2) and general anesthesia without spinal (Group 3). Results: NRS was lower in the spinal anesthesia groups (Groups 1 and 2) than in the general anesthesia group (Group 3) for every time point but at 48 h. The addition of local anesthetics conferred a small but significant NRS decrease ( Adequate pain management for major gynecologic surgery is a key factor to decrease postoperative morbidity and increase patient satisfaction. Uncontrolled postoperative pain in this setting could result in a broad spectrum of harmful consequences, including increased morbidity, delayed hospital discharge and a higher incidence of persistent chronic pain ,2.Indeed, pain can modify a patient’s endocrine response by increasing catecholamines and cortisol levels and may amplify autonomic reflexes, triggering hypertensive crises or vagal syndromes which may result in severe complications during and after surgery. Furthermore, high levels of postoperative pain can negatively influence many “soft” outcomes, including limitation of physical functions, sleep quality and psychological status ,4,5,6.Despite the introduction of several guidelines, postoperative pain continues to be inadequately treated in gynecologic patients and poor pain control may reduce mobilization and significantly correlates with lower long-term quality of life and prolongation of hospital stay ,7,8,9,10On the other hand, side effects of pain treatments  are common in the immediate postoperative period: They can be severe and adversely affect patients’ postoperative recovery quality and patients’ satisfaction.The ERAS guidelines represent a gold standard for the perioperative management of patients undergoing benign and oncological gynecological surgery based on the data obtained from the best clinical evidence available ,7,8.However, the optimal analgesic regimen for gynecological surgery with laparoscopy or mini-laparotomy is still the object of debate. Managing postoperative pain appropriately with a strategy tailored to the patient’s physical status and the specific gynecologic procedure, preventing and managing analgesia-related side effects, is crucial to optimize postoperative rehabilitation and to reduce hospital costs.In literature, there has been increasing interest in the efficacy and safety of spinal anesthesia and intrathecal morphine as an adjunct to general anesthesia (blended) and for postoperative pain relief: Regional anesthesia is an effective way to increase pain control and minimize side effects of systemic opioid medications ,13,14,15In obstetrics and gynecology, spinal anesthesia has become the gold standard for cesarean section and, in some patients, for vaginal hysterectomy. On the other hand, some previous studies have found no benefits from the neuraxial blockade, and general anesthesia is still the most widely used technique for abdominal hysterectomy .The aim of this study was to assess the efficacy and safety of intrathecal administration of morphine with or without local anesthetic as a component of blended anesthesia compared to balanced general anesthesia in patients undergoing laparoscopic or mini-laparotomic hysterectomy with or without lymphadenectomy for ovarian, endometrial or cervical cancer or for fibromatosis.This observational retrospective study was approved by an independent Ethic Committee . Written informed consent was obtained from each patient enrolled. This article adheres to the applicable STROBE guideline.This study was conducted in the gynecological operating rooms and ward of the IRCCS Policlinico Agostino Gemelli Foundation of Rome, Italy; data were collected from 1 January 2019 to 31 December 2021.Data were retrospectively collected from the acute pain service registry (no randomization was performed): All patients were followed by institutional Acute Pain Service and have been included in an electronic registry. We included adult ASA 1 to 3 patients scheduled for laparoscopic or mini-laparotomic hysterectomy (with an incision below the belly button), with or without lymphadenectomy for ovarian, endometrial or cervical cancer or for fibromatosis. Exclusion criteria were age below 18 years, ASA > 3, previous chronic use of analgesics, psychiatric disorders, laparotomic surgery with incision above the belly button and surgery extended to the upper abdomen for the presence of cancer localizations .The cohort of patients was retrospectively divided into three groups according to the anesthetic management: general anesthesia and spinal with morphine and local anesthetic (Group 1), general anesthesia and spinal with morphine (Group 2) and general anesthesia without spinal (Group 3).According to institutional protocols, in an outpatient ambulatory setting, patients were previously advised by an anesthesiologist that, as an adjunct to general anesthesia, they could receive spinal anesthesia before the induction of general anesthesia for postoperative pain management. On the day of surgery, the antalgic procedure was performed after the patient’s consent: Spinal anesthesia was performed in a sitting or lateral position, after appropriate skin disinfection with alcoholic 2% chlorhexidine and local anesthesia (2% lidocaine 3–5 mL), with a 25 G Whitacre needle at the L2-L3, L3-L4 or L4-L5 subarachnoid space, with equipotent doses of local anesthetics (0.5% isobaric levobupivacaine or 0.5% hyperbaric bupivacaine or 0.5% isobaric ropivacaine) and intrathecal opioid  or with intrathecal opioid only , depending on institutional protocol and the choice of the anesthesiologist in the operating room. The sensory level with pinprick was tested after 1 and 5 min in the supine position, in case of use of local anesthetic.Afterwards, general anesthesia was induced with sufentanil 0.1–0.2 mcg/kg i.v., propofol 1.5–2 mg/kg i.v. and rocuronium bromide 0.6 mg/kg i.v. and subsequently maintained with inhalation anesthetic and opioids (sufentanil) keeping a MAC of 0.8–1.5 after endotracheal intubation. On the other hand, anesthesiologist performed only balanced general anesthesia according to the institutional protocol.Dexamethasone 4 mg and ondansetron 4 or 8 mg were administered to all patients to reduce postoperative nausea and vomiting. Paracetamol 1 g four times daily and ketorolac 30 mg two times daily were prescribed postoperatively, if not contraindicated, in all the patients and additional medications  were administered as needed. Abdominal wall block (Transversus Abdominis Plane or Quadratus Lumborum block) or wound infiltration was also performed if spinal anesthesia had not been executed, according to the institutional protocol.For each patient, age, weight, height, ASA (American Society of Anesthesiologists) classification, preoperative medications, type and duration of surgery, hemodynamic parameters during surgery, intraoperative drugs and analgesic technique were recorded. After the end of the surgery, patients were examined at regular intervals: after awakening before leaving the operating room, before the recovery room’s discharge and at 6, 12, 24 and 48 postoperative hours. Assessment of postoperative pain, using NRS , both at rest and with movement, was measured at each time  and the highest NRS was registered as the primary outcome. The regular assessment also included the following parameters: sedation , PONV (postoperative nausea and vomiting), itching, motor block (Bromage classification), metallic taste in the mouth, speech disorders, visual disturbances, tinnitus and arrhythmias, further doses of analgesics as needed in addition to the hourly prescription of paracetamol and ketorolac, paralytic ileus and mobilization of patients in the postoperative period.Additionally, the length of stay in the recovery room and hospital discharge were recorded for each patient.Data were reported as mean ± standard deviation for continuous variables or cases (percentage) for categorical variables. Continuous variables were tested for homogeneity of variances with Levene’s test and differences among groups evaluated by one-way ANOVA or Kruskal–Wallis as appropriate; pairwise comparisons among the means of two groups were performed with Bonferroni correction, and no pairwise comparison was needed for variables tested with Kruskal–Wallis. Categorical variables were analyzed with a chi-square test; pairwise comparisons among groups were made on a logistic regression model for the binary outcome, and Bonferroni correction was used. Repeated measurements in the first two postoperative days were evaluated with a linear mixed model for NRS scores (continuous) and a generalized linear mixed model for PONV and pruritus . Fixed factors included groups and time, and random factors included the patient. To account for differences in intraoperative opioids and rate of mini-laparotomy, the latter were also included as fixed factors in the models. A multivariate logistic regression was used to evaluate the impact of various factors on the occurrence of intraoperative hypotension.p value was <0.05. All analyses were performed with R Statistical Computing, version 4.1.Statistical significance was considered when the n 240), general anesthesia and intrathecal morphine  and general anesthesia without spinal anesthesia . Intrathecal morphine administration ranged from 50 to 100 mcg (100 mcg in more than 95% of patients), while intrathecal local anesthetic could be one of isobaric levobupivacaine , isobaric ropivacaine  and hyperbaric bupivacaine .A total of 644 patients undergoing hysterectomy were retrospectively included in the present analysis. They were further subdivided into three groups according to the anesthetic management: general anesthesia and intrathecal morphine and local anesthetic . Baseline characteristics of the population and relevant surgical procedures are given in p < 0.001, groups p < 0.001, time:group interaction p < 0.001). The addition of local anesthetics conferred a small but significant NRS decrease (p < 0.05). The time course of postoperative pain scores is shown in p < 0.001).Intraoperative management is also displayed in p < 0.001) and type of incision .Accordingly, 33.6% of Group 3 patients needed a rescue analgesic therapy in the first 24 h vs. 3.8% in Group 1 and 4.3% in Group 2. In a multivariate linear mixed model, including the amount of intraoperative sufentanil and the rate of mini-laparotomy as potential confounders, the time course of NRS scores was dependent only on the anesthetic technique , intravenous morphine administration  and ketamine administration . Also, more patients in Group 3 received either a PCA with morphine  or an elastomeric pump with tramadol .A higher percentage of patients in Group 3 received additional techniques for postoperative pain control, including abdominal wall block or wound infiltration , while PONV was only slightly more frequent in Group 1 (OR 3) and Group 2 (OR 2.3) than in Group 3 (p = 0.001).On the other hand, motor blockade (Bromage score > 1) was observed in up to 39% of Group 1 patients immediately after surgery but was negligible after 6 h . As showp < 0.001), with the resulting increased need for vasopressors  and inotropes . On the contrary, fluid management was not significantly different among groups, with similar amounts of crystalloids, albumin and red blood cell transfusions. In addition, the urine output at the end of surgery was remarkably similar among the groups  and age (OR 1.04 per year p = 0.002), but not BMI, baseline hypertension, ASA physical status and type of incision. Indeed, the mean age of patients with significant intraoperative hypotension was significantly greater . Hypotension, defined as MAP  < 65 mmHg lasting more than 5 min, was more frequent in patients receiving spinal anesthesia, especially with local anesthetics . No differences were noted in postoperative mobilization or duration of ileus. A higher percentage of patients receiving spinal anesthesia was discharged on postoperative day 2  (Postanesthesia care unit (PACU) discharge criteria, including pain control, degree of motor blockade, PONV and pruritus, were met earlier in the spinal anesthesia groups than in the general anesthesia group  , but theWith regard to side effects related to the spinal, in this cohort of patients, we recorded one postdural puncture headache and one patient reporting a transient loss of sensibility at the level of the thigh which resolved after four weeks.Gynecological surgeries are some of the most frequent surgeries; however, 4.7–26.2% of women experience chronic postoperative pain . AdequatThe primary finding of this large retrospective analysis was that subarachnoid morphine with or without local anesthetic was effective in improving postoperative pain control following laparoscopic or mini-laparotomic hysterectomy, in reducing intraoperative opioid consumption, in decreasing postoperative rescue analgesics consumption and the need for any additional analgesic technique.Indeed, all groups in the study achieved acceptable pain control at each visit (NRS < 4): Patients who did not receive subarachnoid anesthesia needed a greater amount of intraoperative opioids, postoperative rescue analgesics and additional techniques were used to manage pain in the perioperative period. Nevertheless, pain scores in the subarachnoid anesthesia groups were always lower throughout the study period, even after accounting for major confounding factors (type of incision).This result revealed that the spinal block was effective in reducing postoperative pain in our patients and allowed a significant opioid-sparing effect, with an expectable reduction in associated side effects. This outcome is consistent with previous findings in other surgeries: Levy BF et al. found that spinal anesthesia with intrathecal morphine may facilitate early mobilization in colorectal surgery ; similarMoreover, in accordance with previous studies ,24,25,26The analgesic effect of subarachnoid administration of morphine lasts for about 24 h while the addition of local anesthetic produces an effect for about 6–12 h .It is important to note that, while it is well known that neuraxial blocks have demonstrated efficacy regarding improved pain control and reduced postoperative opioid consumption in open surgery, the literature is still scarce in laparoscopic or mini-laparotomic surgery (with incision below the umbilicus) with expected postoperative pain from moderate to severe. However, these potential benefits must be weighed against the potential risks of neuraxial anesthesia, including possible delayed time to ambulation and voiding, and increased hospital length of stay .Furthermore, it must be pointed out that the spinal technique is easier to perform and more manageable than peridural catheter placement; therefore, it seems to be appropriate for this type of surgery (laparoscopy or mini-laparotomy) as a component within a multimodal strategy.Additionally, the motor block induced by the local anesthetic resulted in better pain control without interfering with patient’s mobilization in the ward. Adding local anesthetic to spinal block produced a relevant motor blockade in a significant group of patients (Bromage score > 1 in up to 39% of Group 1 patients) immediately after surgery, but the motor blockade was negligible after 6 h with no effects in postoperative mobilization. Also, no differences in postoperative ileus were registered.On the other hand, it must be highlighted that adding local anesthetic to intrathecal morphine was associated with a benefit in pain control, at the price of increased intraoperative events and the need for vasopressor. Hypotensive events lasting more than 5 min (MAP < 65 mmHg) were significantly more frequent in patients receiving spinal block with local anesthetics with the resulting increased need for vasopressors and inotropes (norepinephrine and ephedrine). On the contrary, fluid management was not significantly different among groups, with similar amounts of crystalloids, albumin and red blood cell transfusions; also, the urine output at the end of surgery was similar among the groups. We conducted a multivariate logistic regression to establish factors associated with intraoperative hypotension: In our patients, the type of anesthesia and age, but no other features, were associated with hypotension. We recommend individualizing anesthetic strategy on the patient’s physical status and age to properly choose in which patient to administer spinal block with local anesthetics: It seems reasonable to avoid spinal block with local anesthetic in elderly, dehydrated patients or in patients at risk for hemodynamic instability.Complications directly related to spinal procedure were rarely observed: The main side effects of subarachnoid analgesia were pruritus and PONV, while PDPH and neurological sequelae were uncommon. The incidence of pruritus was 3–4 times higher until 24 postoperative hours after administration of intrathecal morphine, while PONV was only slightly more frequent in patients receiving spinal, and no differences were registered after PACU discharge. These results are in accordance with other studies: The main disadvantages of intrathecal morphine include nausea, pruritus, urinary retention and doses greater than 0.2 mg may increase side effects without additional benefit . Interestingly, earlier PACU discharge was possible when spinal anesthesia was administered with a significant reduction in time spent by the patient in the recovery room and the work of the staff who assisted her; moreover, a higher percentage of our patients receiving spinal block was discharged home on postoperative day 2, but in this case, we failed to find a significant independent association with the type of anesthesia . Although this is not the purpose of the retrospective analysis, a reduction in personnel work in PACU and ward, and a reduction in hospital costs in treating our patients, is predictable.This study has also important limitations due to the retrospective design, but the large cohort study suggests that spinal block with morphine alone or with local anesthetics may be a simple and very fast way to confer an advantage in pain control following laparoscopic or mini-laparotomic hysterectomy. Another substantial limitation of the study is the higher presence of patients undergoing mini-laparotomy in the general anesthesia group compared to the spinal groups; mini-laparotomy under the umbilicus was performed in some cases by the surgeon to extract the uterus at the end of the surgery. The visceral manipulation during surgery was similar in all the groups and the duration did not differ among the groups. In any case, the multivariate analysis considered this confounding factor, and its effect on pain scores was overall low but still significant. Randomized controlled trials should be developed to better define the most effective combinations and doses of intrathecal analgesics in laparoscopic and mini-laparotomic hysterectomy.This large retrospective study shows that intrathecal administration of morphine with or without local anesthetic as a component of blended anesthesia is effective in improving postoperative pain control following laparoscopic or mini-laparotomic hysterectomy, reducing intraoperative opioid consumption, decreasing postoperative rescue analgesics consumption and the need for any additional analgesic technique. We recommend managing postoperative pain with a strategy tailored to the patient’s physical status and the type of surgery, preventing and treating analgesia-related side effects.


Specialized pro-resolving mediators (SPMs), including 18-HEPE, 17-HDHA, and 14-HDHA are recognized as potentially therapeutic in inflammatory diseases because SPMs regulate the inflammation process, which leads to, for example; swelling and the sensation of pain. In osteoarthritis (OA), chronic pain is described as the symptom that reduces patients´ quality of life (QoL). The GAUDI study evaluated the efficacy of SPMs supplementation in reducing pain in the symptomatic knee of OA patients.This randomized, multicenter, double-blind, and placebo-controlled parallel-group pilot study was performed in Spain and conducted on adults 18–68 years old diagnosed with symptomatic knee OA. Patients were enrolled in the study for up to 24 weeks, which included a 12-week intervention period and a follow-up visit on week 24. The primary endpoint was pain change measured through a Visual Analog Scale (VAS). Secondary endpoints included: Pain change evaluation, stiffness, and function according to the WOMAC index; assessment of constant, intermittent, and total pain according to the OMERACT-OARSI score; evaluation of changes in health-related QoL parameters; the use or not of concomitant, rescue, and anti-inflammatory medication; and safety and tolerability assessments.Patients were enrolled in the study from May 2018 to September 2021. VAS pain score was evaluated in the per protocol population (n = 51 patients), in which we observed a statistically significant reduction after 8 weeks (p = 0.039) and 12 weeks (p = 0.031) of treatment in patients consuming SPMs (n = 23 subjects) vs. placebo (n = 28 subjects). In line with the OMERACT-OARSI score, intermittent pain was reduced after 12 weeks with statistical significance (p = 0.019) in patients treated with SPMs (n = 23 subjects) vs. placebo (n = 28 subjects). Functional status as WOMAC score did not significantly change after SPMs or placebo consumption. Notably, patients consuming SPMs showed improvements in all five aspects of the EUROQoL-5, including a significant improvement in the usual-activities dimension. None of the patients required rescue medication, nor were any adverse events reported.These findings suggest that sustained SPMs consumption reduces pain in OA patients while also improving their Quality of Life. These results also support the safety profile of SPMs supplementation.Trial registration NCT05633849. Registered 1 December 1 2022. Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT05633849The online version contains supplementary material available at 10.1186/s12967-023-04283-4. Osteoarthritis (OA) is the most common form of arthritis and a significant cause of pain, functional disability, and socioeconomic cost worldwide. OA is a disease that involves inflammatory, mechanical, and metabolic factors. All these lead to pathological changes across different weight-bearing joint tissues, severely and particularly affecting cartilage tissue , 2. ChroInfiltration of immune cells and release of pro-inflammatory mediators activate different inflammatory pathways in joints. These lead to the release of pro-nociceptive molecules, which induce peripheral sensitization , 7. SeveAt the cellular level, SPMs act via specific receptors that promote macrophage phagocytosis of: pathogens, apoptotic cells, and cellular debris, that precede and is necessary for tissue regeneration. SPMs also cease infiltration of pro-inflammatory immune cells, counter-regulate pro-inflammatory mediators, and increase the production of anti-inflammatory mediators . ResolviDespite OA´s prevalence and burden, its standard treatment still involves the use of non-steroidal anti-inflammatory drugs (NSAIDs), which lack sufficient efficacy and present multiple side effects. With limited pharmacological options, in many cases joint replacement is considered as the only treatment option , 7, 34. In this study, the effect of consuming an SPMs enriched oil has been clinically evaluated in the context of pain in patients with OA. This randomized, double-blind, placebo-controlled trial sought to assess the efficacy of SPMs 12-week consumption in reducing pain in patients with symptomatic knee OA.The GAUDI study was a randomized, multicenter, double-blind, placebo-controlled, parallel-group pilot study conducted in 5 Spanish centers in compliance with the World Medical Association Declaration of Helsinki, all its amendments, and national regulations. The Independent Ethic Committee of Hospital Universitario La Paz  approved this study. All patients gave their written informed consent.The study duration per patient was up to 24 weeks consisting of a screening period, a treatment period with monthly visits from the start of the study until week 12, and a last follow-up visit on week 24 conducted by telephone call  or olive oil placebo (placebo group) after breakfast and two 500 mg softgels after dinner for a total of four softgels of SPMs or placebo per day during the first 6 weeks of the study. During the last 6 weeks, participants were instructed to take one softgel after breakfast and one after dinner for a total of two softgels of SPMs or placebo per day. Thus, the treatment period lasted in total 12 weeks per patient.Eligible patients for the study were adults between 18 and 68 years old that were diagnosed with symptomatic knee OA (according to the American College of Rheumatology [ACR]) and primary knee OA with both confirmed scores of 2–3 on the Kellgren and Lawrence radiological scale  and 5 orThe primary endpoint was the change in pain measured as VAS score before supplementation and VAS score on week 12 of supplementation. Secondary endpoints included the comparison in pain change, stiffness, and joint function according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) between SPMs and placebo groups before supplementation to week 12. In addition, the assessment of constant, intermittent, and total pain according to the OMERACT-OARSI score was considered. Changes in health-related QoL scores measured by the EUROQoL-5 questionnaire  between Three patient populations were considered in analyses: (i) The per protocol (PP) population, including all randomized patients who received at least one treatment dose and had all primary endpoint measurements and no major protocol deviations; (ii) the intention-to-treat (ITT) population, including all randomized patients; (iii) and the safety population, with all randomized patients who received at least one dose of the study treatment. The PP population dataset was the only population considered for the primary analysis.For univariate analysis, the quantitative variables were described using central tendency and dispersion measures, including mean, standard deviation (SD), median and interquartile range (IQR). To define qualitative variables, total counts and percentages were used.For bivariate analysis between distinct subjects, quantitative variables were analyzed using the Student's t-test for independent samples or the Mann–Whitney U test when samples were not normally distributed. Qualitative variables were analyzed using the Chi-square test or the Fisher test. For intra-subject variables, quantitative variables were analyzed using the Student's t-test or the Wilcoxon signed-rank test, depending on whether the samples were or were not normally distributed.Missing data were discarded in the analyses, and a significance level of 0.05 was used in statistical testing. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 22.0 .One hundred patients were recruited in the GAUDI study from May 2018 to September 2021. Fifteen enrolled patients were excluded from the study because they did not fulfill the selection criteria. Therefore, 85 patients were included in the analyses and constituted the ITT population. The PP and safety populations comprised 51 and 52 patients, respectively. In the PP population, 23 patients were assigned to the SPMs group and 28 to the placebo group.Patients characteristics upon inclusion are presented on Table There was a statistically significant lower pain VAS score in the SPMs group compared to the placebo group after 8 weeks  and 12 weeks  of treatment . From weeks 12–24, pain VAS score changes increased by 50.1 ± 115.60% in the SPMs group and 2.5 ± 65.69% in the placebo group, respectively . On week 24, the pain VAS score was similar between placebo and SPMs groups .Constant, intermittent, and total pain, as measured with the OMERACT-OARSI method, did not significantly vary between patients receiving SPMs or placebo at any time. The intermittent pain changes significantly decreased by: 30.6 ± 29.30% in the SPMs group and by 18.1 ± 25.53% in the placebo group    Table . PatientNone of the patients required rescue medication Table . Before Only two AEs were reported in one patient from the SPMs group (lameness and locked knee), which were mild and not related to the study treatment. These did not require any action from the research team and were resolved. None of the patients withdrew from the study.The results of this randomized, double-blind, placebo-controlled study imply that oral supplementation with SPMs reduces pain and improves QoL in patients with symptomatic knee OA. While a placebo effect is observed in clinical variables, this is not as significant as the effect of SPMs consumption. Following a dose reduction from 2000 mg/day to 1000 mg/day from weeks 6 to 12, patients receiving oral supplementation with SPMs reported a statistically significant reduction in pain after 8 and 12 weeks of treatment compared to patients in the placebo group. Also, we observed a trend, such as the reduction in the pain VAS score up to week 12 and changes in VAS score from weeks 12 to 24, that added to the impact of continuous SPMs consumption. Altogether, these results support the recommended dual dose for OA patients.OA patients identify two types of pain: constant background pain and intermittent severe pain . The latPain reduction associated with SPMs administration is in line with previous studies pertaining to inflammation resolution mechanisms. Preclinical data from different animal models of osteoarthritis, acute inflammatory pain, and chronic adjuvant-induced arthritis support the pain-relieving properties of 17-HDHA and resolvin D1 exogenous administration , 45. NotTo our knowledge, this is the first-in-human study evaluating possible residual effects of SPMs months after treatment. Our results do not support a long-lasting residual effect of SPMs consumption on chronic pain 12 weeks after the completion of treatment, suggesting the need for continuous supplementation to maintain clinical benefits. Preclinical studies, however, have evaluated the long-lasting effects of SPMs. A study in surgical pain in a mouse model demonstrated that intrathecal-injected resolvin D1 showed an analgesic effect for up to 30 days . AnotherEssentially, chronic pain involves central and peripheral neurological mechanisms. Preclinical studies have shown that SPMs administration dampens inflammatory pain . In addiIn this study, SPMs supplementation did not change concomitant, rescue, and anti-inflammatory medication use. Also, no adverse events related to supplementation nor any tolerability issues were reported in this study. These data support the favorable safety record of SPMs supplementation with the administered dose, which agrees with previous studies .Some limitations of this study included the modest sample size, which might have constrained the statistical significance of the results and masked the full clinical potential of SPMs consumption by OA patients. Despite the low number of participants, there is a general trend of improvement in most of the assessed clinical parameters, supporting the potential benefits to be confirmed in a larger sample number. Another limitation is the use of olive oil softgels as placebo. Olive oil has been reported to have clinical effects on OA patients, as previously reported in randomized controlled trials , 52. AllOne future study will involve the analysis of the biochemical parameters from plasma and serum samples of the patients on this study, including SPMs and cytokines. Other studies could be performed on assessing pain reduction in patient subpopulations. For example, studying the effect of SPMs consumption in patients with one specific degree of osteoarthritis according to the Kellgren and Lawrence classification. Patients with other diseases that also experience chronic pain may benefit from SPMs consumption, though; studies that support that need to be rigorously performed. As individual SPMs are made available in their purest forms, future studies could be performed to treat joint degeneration locally, instead of systemically.This randomized, double-blind, placebo-controlled study evaluates for the first time the effect of continuous oral SPMs consumption on an adult population of symptomatic knee OA patients. SPMs supplementation reduced pain and improved the quality of life of OA patients. Our results do not support a long-lasting residual effect of SPMs after treatment, suggesting the need for continuous SPMs supplementation to maintain some of the clinical benefits. The results from this study support the favorable safety record of SPMs-enriched oil consumption.Additional file 1: Table S1. Blood test results (N = 51).


Complex orofacial pain disorders, such as trigeminal neuralgia (TN) and atypical facial pain (AFP), can be excruciating and debilitating during attacks. Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, is a powerful analgesic that has been used to treat various chronic pain conditions, but its role in treating complex facial pain has only been recently explored. In this retrospective case series, we reviewed the efficacy of continuous ketamine infusion for 12 patients with facial pain refractory to medical treatment. Patients who presented with a diagnosis of TN were more likely to have significant and sustained pain relief after receiving ketamine infusion. By contrast, those who did not respond to the treatment were more likely to have a diagnosis of AFP. The current report suggests a fundamental difference between these two facial pain disorders in their respective underlying pathophysiology and supports the use of continuous ketamine infusion for refractory TN, but not AFP. Orofacial pain is a class of complex and debilitating pain conditions that are challenging to diagnose and treat . The IntTN, one of the most common forms of severe orofacial pain, is characterized by recurrent severe paroxysmal stabbing or electric shock-like pain in the trigeminal nerve distribution ,4. The cOn the other hand, atypical facial pain (AFP), also known as persistent idiopathic facial pain, is a diagnosis of exclusion. It is characterized by persistent facial pain that is beyond the trigeminal nerve distribution and is often associated with neuropathic pain quality, such as dull, aching, or nagging . UnfortuHowever, options for medical management remain limited when TN or AFP patients become refractory to their respective first-line treatments. Ketamine infusion has shown promise in treating neuropathic pain. Being an analgesic and sedative agent that acts primarily as a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors and with endogenous opioid receptors at high thresholds, ketamine is thought to limit central sensitization through plasticity and the descending antinociceptive pathway -11. ContThis study was performed in accordance with relevant guidelines and regulations. The research protocol was approved by the Institutional Review Board Committee at Stanford University (protocol #52966). A total of 280 patients were admitted to the inpatient chronic pain service at the Stanford Medical Center for continuous ketamine infusion from 2011 to 2018. Inpatient ketamine infusion is a part of the standard treatment protocol at Stanford University Hospital and is regularly offered to patients with resistant facial pain who have failed pharmacological management. Of the 280 patients who received ketamine infusion, 12 patients were identified for further review with the specific hospital admission diagnosis of “refractory facial pain,” “atypical facial pain,” or “trigeminal neuralgia.” These 12 patients formed the basis of this retrospective pilot study. These patients’ records were also associated with descriptions of “facial pain,” “oral pain,” “facial CRPS,” or “trigeminal neuropathy.” Given the classification of “persistent idiopathic facial pain” did not exist before 2020, this search term was omitted. Patients’ electronic medical records were reviewed for demographic data, medical history, psychiatric history, body mass index (BMI), medications prescribed prior to admission, prior procedural interventions, and medications received during admission.All 12 of these patients were admitted for five to seven days of continuous ketamine infusion according to the institutional protocol, which started ketamine infusion (non-weight-based) at 10 mg/h and titrated up to 50 mg/h based on the treatment efficacy and patient tolerance. Pain scores were recorded every four hours, and vitals were recorded every six hours. Average daily pain scores throughout the admission were calculated for each patient. Based on the methods recommended in the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) guidelines, “responders” were defined as patients with a significant reduction (50% or greater) in the pain score or a pain score of 0 at the time of discharge and sustained pain relief for more than two weeks . The remAdverse effects during hospital admission were documented and included psychomimetic symptoms , somnolence, pre-syncope, nausea, vomiting, and elevated blood pressure. Statistical analyses were performed using GraphPad Prism software, version 9. Quantitative data were presented as mean ± standard deviation. Qualitative data were expressed as frequency and percentage. Student’s t-test of significance for independent samples was used for comparing two means. Patient characteristics  between the responder group and the non-responder group were compared. Comparisons between patients’ pain scores were done with the Mann-Whitney test. Chi-square tests were performed for comparisons between categorical data . A p-value less than 0.05 was considered statistically significant.Patient demographic data are summarized in Table Differences in the treatment protocol and patient characteristics between the responder and non-responder groups were investigated. Interestingly, there were no significant differences in infusion duration or maximum infusion rate between responders and non-responders. However, the weight-corrected infusion rate showed that the responders required a lower dose of ketamine to achieve adequate pain relief  as shown in Table To better characterize the degree of pain relief from continuous ketamine infusion, the change in pain scores of the responder group was compared with previously published data . AdoptinThe side effects of ketamine infusion were minimal and temporary. Among the 12 patients during the admission period, two patients reported pre-syncopal symptoms such as lightheadedness and dizziness, one experienced somnolence, one experienced hallucination, one had nausea, and one had elevated blood pressure. These symptoms were self-limiting within hours once infusion rates were adjusted to a lower dose or stopped completely. The as-needed medications used by the patients included clonidine and lorazepam. There were no complaints of long-term sequelae on follow-up appointments.Orofacial pain is challenging to treat, in part, because of a lack of pathophysiological understanding of the subtypes of orofacial pain . In the There is limited research to guide the use of continuous or intermittent ketamine for chronic neuropathic or nonneuropathic chronic pain . InpatieAlthough failed to reach statistical significance, our current data demonstrated a trend that younger participants respond more favorably to ketamine infusion than older participants. There are no published studies that examine age as an independent factor in ketamine infusion for complex orofacial pain disorders. In the studies of serial ketamine infusions for treatment-resistant depression, younger age may be associated with a faster response but may not be associated with durability or efficacy . In ketaOne of the advantages of an inpatient continuous ketamine infusion is that it allows trained staff to titrate ketamine to the desired pain-relieving effect for each patient while monitoring for adverse events from ketamine administration. This allows for close inpatient monitoring of any psychiatric symptoms. The incidence of ketamine addiction is unknown due to the lack of large-scale studies, but nevertheless, ketamine's potential for addiction should be considered when patients are treated with intermittent IV infusions ,23. In tOverall, our study suggests that continuous ketamine infusion provides a greater and longer pain relief for patients with refractory TN than for those with AFP. However, there are several major limitations, given the retrospective and case-series nature of the study. First, the long-term effects of five to seven days of continuous ketamine infusion remain unknown, given the small sample size and the short-term follow-up period. The lack of a control arm for the responder group could further confound the interpretation of the data. Finally, given the clinical sources required for inpatient infusion treatment, the missing data on treatment cost can limit its application in settings with scarce resources. Research on technical parameters of ketamine infusion, including dosing, length, and frequency of infusion, will also be required. Future randomized controlled studies with larger sample sizes and longer follow-up periods would be needed to further delineate the effects of continuous ketamine infusion as a therapy for refractory facial pain.


Subsequent to coronary angiography, procedures performed to prevent bleeding may cause pain in the patient. In this study, we aimed to determine the effect of acupressure on pain level and hemodynamic parameters in patients undergoing coronary angiography.n = 62) received acupressure on the LI4 , PC6 (three fingers above the wrist), and LI11  points for 15 min 2 h after angiography, while the control group (n = 62) received no acupressure. Data were collected using the visual pain scale (VAS) and hemodynamic parameters , monitoring form before, immediately after, and at 10, 20, and 30 min after acupressure.In this prospective, a two-arm (1:1), randomized controlled trial was conducted, with 124 patients undergoing coronary angiography included. The randomly assigned study group . When the groups were compared, it was found that the VAS score of the study group before angiography was significantly higher than that of the control group, but lower than the control group immediately after acupressure, and at 10, 20, and 30 min after acupressure. In addition, it was determined that acupressure was significantly higher in DBP and RR in the study group compared to the control group at 20 and 30 min; it was not effective in terms of SBP, HR, and SpOThe results of the study indicated that patients reported moderate pain after coronary angiography, and that acupressure was effective in reducing the pain level, but affected only the DBP and RR hemodynamic parameters. Since the study was single-centered and followed for a short time, it is recommended to conduct new studies with a longer duration. One of the hypotheses of this study is that acupressure used in patients affects pain levels. The other hypothesis of this study is that acupressure used in patients affects hemodynamic parameters.Coronary artery disease is the most common cause of cardiovascular disease , which r < 0.05) . Numerou < 0.05) , 12–14.  < 0.05) –18. In p < 0.05) –18; howeThis study was conducted as a prospective parallel two-arm [1:1] randomized controlled experimental study. The study sample consisted of 124 patients who underwent CA in a public hospital between 25 November 2022 and 30 December 2022. Taking the study of Vagharseyyedin et al. (2022) as a reference . Compliance of the patients with the inclusion criteria was determined by the cardiologist researcher (BD). When the researcher (TÇY) attended the patient for application of acupressure, he opened the envelope and learned which group the patient was in. Since acupressure was to be applied only to the patients in the experimental group, the patients who received and the researcher (TÇY) who applied acupressure could not be blinded due to the nature of the study. The researchers (BD and CK) who collected the data before and after the application were blinded because they did not know which group the patients were in. In addition, when the study was completed, the data were transferred to a computer by a statistician who did not know about the A and B groups; the data were analyzed, and the findings were reported by a statistician independent of the study. Thus, the data analysis and statistics phase was also blinded.2).The primary outcome measure of the study was the effect of acupressure application on patients' pain level. The secondary outcome measure of the study was the effect of acupressure application on patients' hemodynamic parameters  of the patients : The VAS consists of a 10 cm long line with subjective descriptive statements at both ends of the scale (0 cm = absent and 10 cm = extremely present) (present) . The indpresent) , 19.Hemodynamic Parameters Monitoring Form: The Hemodynamic Parameters Monitoring Form was prepared to record the values of SBP, DBP, HR, RR, and SpO2 of the control and experimental group patients before, immediately after, and at 10, 20, and 30 min after the intervention.Two hours after CA, patients in the experimental and control groups were first asked to sign an informed consent form about the study. Afterwards, the Descriptive Characteristics Form, VAS, and Hemodynamic Parameters Monitoring Form were completed.In the clinic, 10 cc prilocaine hydrochloride local anesthetic drug was administered subcutaneously to the femoral region before CA. Considering that the half-life of this drug is on average 2–4 h , and as Acupressure points   22–24) –24 22–24The control group was not provided with any treatment other than routine treatment and care.2 values were evaluated with a portable monitor  and recorded on the Hemodynamic Parameters Monitoring Form.In the experimental group, VAS assessments were performed 2 h after CA, immediately after acupressure application, and at 10, 20, and 30 min after the application. Assessments were performed in the control group at the same times as in the study group . At the specified times, SBP, DBP, HR, RR, and SpOχ2 tests. Compliance of the variables with normal distribution was performed using the Shapiro–Wilk test. An independent samples t-test was used for intergroup comparisons of data conforming to normal distribution; a Mann–Whitney U test was used for data not conforming. The significance level of statistical tests was p < 0.05 in all analyses.Descriptive statistics were expressed as frequency, percentage, mean, standard deviation, and maximum-minimum. Categorical variables were analyzed by Fisher–Exact, Continuity Correction, and Pearson-p > 0.05)  .p < 0.05)  and control groups (3.98 ± 1.82) were moderate at the 2nd hour after CA (before acupressure). The pain levels of patients in the experimental and control groups were compared; the average patients pain score the in the study group before the application was significantly higher than that in the control group, and immediately after the application, the average of the VAS scores 10, 20, and 30 min after the application was significantly lower ( < 0.05) .2, but there was a difference for DBP and RR (p > 0.05). The DBP and RR values of the patients in the experimental group were found to be significantly higher than those of the control group 20 and 30 min after the application (p < 0.05)  .In this research, in which the effect of acupressure on the pain level and hemodynamic parameters of patients after CA was investigated, it was observed that patients experienced moderate pain after CA and that acupressure maintained its effect in reducing the pain level for 30 min, but did not affect other hemodynamic parameters except for DBP and RR.Coronary angiography itself, with painful applications such as sandbags or pressurized dressing, applied to the venture area to prevent bleeding, can increase the level of pain by affecting the perception of pain , 14. In In this research, acupressure was applied to the hand (LI4), arm PC6), and elbow bend LI11) points. In previous studies, acupressure was applied to different points on the hand [LI4 , 15–17, , and elb points. Pain that occurs after invasive interventions such as CA  causes s2 values. In addition, the hemodynamic parameters of all patients in the study were within normal ranges. In the literature, a study examining the effect of acupressure on hemodynamic parameters before CA was found (p < 0.05). In contrast to our study, in the aforementioned study, it was found that blood pressure values decreased immediately after acupressure application, at 15 and 30 min (p < 0.05) (p < 0.05)   . In anot < 0.05) . In the  < 0.05) .The emergence of a feeling of relaxation due to the completion of a stressful invasive procedure such as CA in all patients and the decrease in pain over time after the procedure  may haveThe results of this research showed that patients experienced moderate pain after CA and that acupressure applied by healthcare professionals was effective in controlling pain, DBP, and RR values. It may be recommended that acupressure, which is easy to apply, inexpensive, reliable, and has no side effects, should be applied in patients after CA. The fact that only one study was found in the literature in which acupressure was applied after CA shows that more comprehensive, multicenter, prospective, randomized, and controlled studies on this subject are needed.The most powerful aspect of this research is that it is the first study to determine the effect of acupressure on pain and hemodynamic parameters after CA. On the other hand, the discussion of the changes in hemodynamic parameters was therefore limited. In addition, since the study was single-centered, it cannot be generalized to all patients undergoing CA.


Accurate identification of neuropathic pain is necessary for appropriate treatment; however, the relationship between nontraumatic shoulder disorders and neuropathic pain remains unknown. Therefore, this retrospective observational study aimed to investigate the relationship, features, background factors, and prevalence of neuropathic pain among patients with nontraumatic shoulder disorders.  We evaluated 198 patients who visited our outpatient clinic, which specializes in shoulder disorders, from April 2015 to March 2016. The patients' age, sex, affected side, diagnosis, and pain duration were recorded, and the results of physical examination, including passive range of motion, impingement sign, and muscular strength assessments, were analyzed. The presence of neuropathic pain was assessed using the painDETECT questionnaire. Participants were divided into two groups according to the presence of neuropathic pain. Pain intensity was assessed using a visual analog scale, and the patient's mental status was assessed using the short-form McGill Pain Questionnaire and Hospital Anxiety and Depression Scale. The scores were compared between the groups.  Neuropathic pain was observed in 7.6% of patients. The visual analog scale score for pain, short-form McGill Pain Questionnaire score, and Hospital Anxiety and Depression Scale score were significantly associated with the presence of neuropathic pain in the univariate analysis. Patient background factors and physical function were not associated with the presence of neuropathic pain. The prevalence of neuropathic pain in patients with frozen shoulder was 33.3%, which was significantly higher than that in patients with other shoulder disorders.  The occurrence of neuropathic pain may aggravate pain in patients with nontraumatic shoulder disorders. Neuropathic pain was not a rare condition in patients with nontraumatic shoulder disorders, particularly in those with frozen shoulder. The coexistence of neuropathic pain cannot be determined from background factors or physical function. Accurate diagnosis of neuropathic pain is essential in patients with nontraumatic shoulder disorders. Neuropathic pain is defined as “pain caused by a lesion or disease of the somatosensory system”  and is aPhantom pain following limb amputation is a well-known example of neuropathic pain in patients with orthopedic disorders. Recently, neuropathic pain has been associated with nontraumatic orthopedic disorders, such as osteoarthritis of the knee or hip, lower back pain, and rheumatoid arthritis –12. In sTherefore, this study aimed to determine the relationship between neuropathic pain and pain in various nontraumatic shoulder disorders and to identify characteristics and background factors in patients with neuropathic pain in shoulder disorders. We hypothesized that neuropathic pain is negatively associated with pain in patients with rotator cuff tears and in those with various nontraumatic shoulder disorders.The Institutional Ethical Review Board for Medical Research involving human subjects approved this cross-sectional observational study . The research was performed in accordance with the tenets of the Declaration of Helsinki. All participants provided written informed consent after receiving an appropriate explanation of the study.Patients who visited our outpatient clinic, which specializes in shoulder disorders, from April 2015 to March 2016 were retrospectively evaluated. The inclusion criterion was as follows: presence of nontraumatic shoulder disorders, such as degenerative rotator cuff tear or osteoarthritis. The exclusion criteria were as follows: history of previous trauma, previous surgery, or any other treatment to the affected shoulder; cervical spine disorders or neuromuscular disease; bilateral cases; and refusal to participate. The study population comprised 118 male and 80 female individuals : 11.9 years; range: 26–85 years). The mean duration of pain was 8.3 months . Based on the International Association for the Study of Pain definition of chronic pain (pain lasting >3 months), 80 patients had acute pain and 118 had chronic pain.The following patient characteristics were recorded: age, sex, affected side, and duration of pain. Physical examination of participants was conducted to evaluate the passive range of motion (ROM), muscular strength, and impingement signs. The upper extremity ROM was evaluated in four positions , with the patient in the sitting position. The internal rotation ROM was assessed based on the highest spinal segment that patients could reach with their thumb. The spinal segment was converted to a numerical value, as described previously . MusculaPlain radiographs of both shoulders were obtained in anterior-posterior, scapular-Y view, and axial directions. Magnetic resonance imaging (MRI) or ultrasound examination was performed when deemed necessary by the treating physician to evaluate soft tissue status. Computed tomography was performed when it was necessary to evaluate bone morphology.Diagnosis was guided by a combination of physical examination and imaging findings. A rotator cuff tear was identified when a rotator cuff footprint avulsion was visible on MRI or ultrasound. Subacromial impingement syndrome was diagnosed when patients had a positive subacromial impingement sign , 17 withNeuropathic pain is usually diagnosed based on responses to a self-reported questionnaire regarding pain, such as painDETECT , which hPain severity was assessed using a 100 mm visual analog scale (VAS) during the patients' first hospital visit. Patients were asked about their pain intensity over the preceding 3 days, including the day of the first visit. Pain at rest, pain on motion, and pain during the night were assessed separately. Using the questions in the painDETECT, pain at the first visit as well as the most severe pain and average pain experienced in the past 4 weeks before the first visit were also investigated using a numerical rating scale.Patients' distress was assessed on the first visit using the Japanese version of the short-form McGill Pain Questionnaire (SF-MPQ) . The SF-The patients' mental status was evaluated during the first hospital visit using the Hospital Anxiety and Depression Scale (HADS) , which hThe prevalence of neuropathic pain was studied for the entire study population and for patients with each shoulder disorder. First, this prevalence was evaluated in all participants, and then, it was computed and compared for each nontraumatic shoulder disorder.t-test or Mann–Whitney U test. Categorical variables were compared using the chi-squared test or Fisher's exact test.The participants were divided into two groups according to the presence or absence of neuropathic pain: groups with and without neuropathic pain. Patient demographics and all scale scores were compared between these two groups. Continuous variables were compared using the t-tests between the two groups were described to statistically examine the impact of neuropathic pain on pain in patients with nontraumatic shoulder disorders. Furthermore, to determine whether there were any differences in the prevalence of neuropathic pain among patients with five nontraumatic shoulder disorders, the prevalence for each disorder was compared using Fisher's exact test adjusted with Bonferroni's method.As the outpatient data were retrospectively analyzed, no prior power analysis was performed for recruitment. Instead, effect sizes and confidence intervals for P values <0.05.All statistical analyses were conducted using SPSS version 26 . Results are considered statistically significant at A total of 296 patients visited our outpatient clinic during the study period. Of these, 213 had nontraumatic shoulder disorders. Fifteen patients were excluded from the study, as they met the exclusion criteria, had missing data, or did not agree to participate. In total, 93.0% of patients who attended our clinic during the study period with nontraumatic shoulder disorders were included .n = 15). No differences in background factors were noted between patients with and without neuropathic pain (All patients completed all questionnaires regarding demographic characteristics and clinical background, as well as physical examination tests. Neuropathic pain was observed in 7.6% of subjects (hic pain .  Table Pain at rest, pain on motion, and pain during the night were significantly more severe in patients with neuropathic pain. The effect sizes and 95% confidence intervals of the differences between the two groups in mean pain intensity at rest, on motion, and during the night are shown in The prevalence of neuropathic pain was shown to be unevenly distributed according to Fisher's exact test. This prevalence was significantly higher in patients with frozen shoulder than in patients with other shoulder disorders after Bonferroni's adjustment .In this study, we examined the relationship, features, background factors, and prevalence of neuropathic pain in patients with nontraumatic shoulder disorders. The most important findings were that 7.6% of patients with shoulder disorders were affected by neuropathic pain and that neuropathic pain was negatively associated with pain in patients with rotator cuff tears and in those with various nontraumatic shoulder disorders, as hypothesized. The VAS scores for pain at rest, on motion, and during the night and the SF-MPQ and HADS scores were significantly associated with neuropathic pain. There were no differences in background factors or in the results of physical examination between patients with and without neuropathic pain. The prevalence of neuropathic pain in patients with frozen shoulder was significantly higher than that in patients with other shoulder disorders.Phantom limb pain after amputation is a typical example of neuropathic pain in patients with orthopedic disorders, and the pathology may include both peripheral nerve injury caused by surgery and disorders of the central nervous system . ConversKarasugi et al. reported the characteristics of neuropathic pain using the painDETECT questionnaire in patients with rotator cuff tears and identified that the VAS score for pain in the previous 4 weeks was a factor in discriminating neuropathic pain . Ko et aPatients' background factors were not associated with the presence of neuropathic pain, which is consistent with the findings of previous reports that patients' background factors were not correlated with a neuropathic pain component in patients with orthopedic disorders , 33, 36.Pain duration was not correlated with the presence of neuropathic pain. The temporal change in pain signaling is known to contribute to the development of chronic neuropathic pain , 6. In gIn this study, patients with neuropathic pain reported more severe pain at rest, on motion, and during the night. This is consistent with the established clinical characteristics of neuropathic pain in patients with low back pain, carpal tunnel syndrome, and other chronic pain , 36, 39.The SF-MPQ scores were higher in patients with neuropathic pain than in those without neuropathic pain. The SF-MPQ consists of two components that assess both the intensity of pain and an altered mental status. In this study, scores for both the components were higher in patients with neuropathic pain than in those without neuropathic pain. These results may suggest that the coexistence of neuropathic pain aggravates not only the intensity of pain but also the patient's mental health status. Furthermore, the total HADS score and HADS-D score were higher in patients with neuropathic pain than in those without neuropathic pain. Previous studies have described a correlation between neuropathic pain and a depressive state –42; our Previous studies on orthopedic disorders have reported that the prevalence of neuropathic pain is approximately 12%–15% in patients with low back pain , 33 and The symptoms of early stage rotator cuff tear and frozen shoulder are similar. Therefore, it is often difficult to diagnose these conditions based on physical findings alone without MRI results. In this study, when comparing the different shoulder disorders, the prevalence of neuropathic pain in patients with frozen shoulder was more than six times higher than that in patients with rotator cuff tear. Neuropathic aberrations detected by painDETECT can be used as supporting evidence to differentiate between rotator cuff tear and frozen shoulder.This study has some limitations. First, we only used a self-descriptive questionnaire to diagnose neuropathic pain. Future studies should objectively evaluate neuropathic pain, e.g., by confirming the presence of sensory abnormalities consistent with innervation. Second, patients' health behaviors, such as smoking and alcohol consumption, as well as the presence or absence of underlying diseases, such as hypertension and diabetes, were not investigated. Thus, the potential influence of these factors on neuropathic pain in patients with shoulder disorders was not clarified. Third, a multivariate analysis could not be performed owing to the small number of neuropathic pain-positive patients. Fourth, this study was performed at a single institution; therefore, larger multi-institutional studies are needed.Nevertheless, this study revealed that neuropathic pain in patients with nontraumatic shoulder disorders is not a rare condition. This finding may help ensure better pain control in these patients.We assessed the impact, features, and prevalence of neuropathic pain in 198 patients with nontraumatic shoulder disorders. Neuropathic pain was observed in 7.6% of participants. The occurrence of neuropathic pain may aggravate pain in patients with shoulder disorders. However, the coexistence of neuropathic pain could not be detected from the patients' background or physical examination findings alone. Neuropathic pain in patients with shoulder disorders was not a rare condition, particularly in patients with frozen shoulder. Clinicians should ensure that neuropathic pain is accurately diagnosed in patients with shoulder disorders.