Demonstrate that continuous peripheral nerve block (CPNB) may be an alternative with adequate analgesia and a lower incidence of side effects for ischemic pain due peripheral obstructive arterial disease (POAD).Retrospective cohort study with 21 patients with POAD, Fontaine IV graded, with foot pain. Patients were submitted to continuous sciatic nerve block (CSNB), through a perineural catheter. Primary outcomes were pain intensity  and opioid consumption .During CSNB, pain scores markedly decreased in comparison to the pre-block period.CPNB may be a good option for ischemic pain treatment in in-patients, as it provides effective pain control with fewer adverse effects. Peripheral arterial obstructive disease (PAOD) is frequent among the elderly . IschemiContinuous epidural analgesia provides good analgesia, but with possible side effects and limitations of neuraxial manipulation in patients frequently receiving anticoagulant agents . ContinuIn this study, we hypothesized that CSNB may provide adequate management of lower limb ischemic pain. Its aim is to describe how pain intensity evolves with CSNB analgesia in these patients.°- 1.571.917). Written informed consent was obtained from all subjects participating in this study. This article adheres to the applicable Enhancing the Quality and Transparency of Health Research checklist [The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement].This is a retrospective cohort study of patients submitted to CSNB for ischemic pain management. The research was approved by the Hospital Ethics in Research Committee , ischemic pain in the foot and who were waiting for definitive vascular surgery treatment. Exclusion criteria were: patients who did not accepted CPNB as a pain treatment option, non-cooperative patients, those with coagulation disorders, systemic or block site infection, allergies to local anesthetic and difficulty understanding the use of the patient-controlled analgesia (PCA) device, and those who refused to be submitted to peripheral nerve block.® Tuohy, B. Braun, Germany) was inserted, from the lateral side of the thigh, through the biceps femoris muscle, and its tip was located close to the sciatic nerve . A bolus of 5 mL of ropivacaine 0.375% was injected, and an 18G epidural catheter, 50 cm long, was passed through the cannula until 3-4 cm beyond the tip of the needle. The catheter was secured to the skin with suture (Nylon 3-0 thread) and covered with transparent drapes. Another bolus of 5 mL of ropivacaine 0.375% was injected through the catheter under US visualization, for spread evaluation. A PCA pump  was connected to the perineural catheter with ropivacaine 0.2% solution, programmed as: infusion of 5-8 mL/h, bolus of 5 mL, and lock-out interval of 30 min  linear ultrasound (US) transducer  was used to locate the sciatic nerve right above its division into the tibial and common fibular nerves. After anesthesia of the skin , under US guidance, an 18G 100mm needle  and opioids, according to assisting physician’s best judgment .The patients kept the catheter with the PCA device until the definitive treatment of vascular surgery, but, for research purposes, data were registered for the first eight days. Primary outcomes were daily pain intensity  and daily amount of opioid use , on the day before the start of the CSNB, and for the following days under CSNB use. Patients were asked for the lowest, mean and highest pain scores, every day. Other data compared were pain reduction percentage and analgesic treatment satisfaction . Sex, age, height, weight, associated morbidities, physical status by American Society of Anesthesiology (ASA) classification, side effects, neurological symptoms and complications were also registered.Data were registered in an electronic database (REDCap 7.6.10 - © 2018 Vanderbilt University) and presented as mean±standard deviation (SD), or median (minimum - maximum) for continuous variables. Daily pain scores and opioid consumption in the CPNB period were compared to the pre-CPNB period through the Friedman test, using SPSS software version 13.0 for Windows .Patients waited for vascular surgery treatment, while using CSNB, for 3-21 days. Demographic and baseline data are illustrated in Pain scores and satisfaction with analgesic treatment are illustrated in p=0.096) (p=0.014)  . Local ap=0.014) .p=0.176).There was no statistically significant difference for opioid use among the different periods  can occur. In this scenario, regional peripheral analgesia appears to be a viable alternative and with fewer adverse effects, as demonstrated in several postoperative studies . The preOpioid consumption during CSNB did not decrease on the following days. Opioids were prescribed by the assisting physicians, at fixed intervals or PRN. Therefore, even with patient’s pain improved by the CSNB, a reduction of opioid prescription did not occur because they would not risk a possible worsening of pain. As there was no increase in opioid consumption, it can be assumed that CSNB had a positive effect in analgesia.Although analysis showed that pain scores decreased and satisfaction increased during the CSNB period, local anesthetic consumption increased. Possible explanations for these facts are minor migration of the catheter along the period, tachyphylaxis for local anesthetics, or even alternative neural pathways for ischemic pain, which would not be fully blocked by perineural blockades .One important limitation of this study is in its methods. This is the retrospective cohort study. We believe that a prospective randomized controlled clinical trial would be a better type of study to compare CPNB to systemic opioids and adjuvants as analgesic treatments. Even with the theoretical concept suggesting that this may be a better option for PAOD patients , especially in elderly, this hypothesis can only be supported by larger and better designed studies. Our group began to use this analgesic method as an attempt to provide better pain control to these patients, because systemic opioids and adjuvants had led to unsatisfactory results or intolerable side effects. Further studies are needed, including other possible benefits: better surgery results, a reduction in post-operative chronic pain and the prevention of phantom limb pain in cases of amputation.In conclusion, this study demonstrated that the use of CSNB in patients with lower limb PAOD is a viable and effective alternative for ischemic pain treatment, with a milder adverse effects profile.What is knownPeripheral obstructive arterial disease (POAD) usually evolves with severe ischemic pain in the lower limbs.Systemic analgesic drugs are frequently ineffective or cause adverse effects.Continuous peripheral nerve blocks are effective for limb pain in orthopedic surgery.What is newLower limb ischemic pain patients had decreased pain scores when treated with continuous peripheral nerve block.Continuous peripheral nerve block may be a good option for in-patient ischemic pain treatment, with a milder adverse effects profile.Fernandes HS performed the study design, patient recruitment, data collection, regional anesthesia procedures and manuscript writing. Ximenes JLS performed data collection, data analysis and manuscript writing. Taguchi PK performed data collection and manuscript writing. Espada EB performed patient recruitment and helped on study design. Gouvêa AL performed data collection. Vieira JE helped with study design, data analysis and manuscript writing. Ashmawi HA helped with study design and manuscript writing. All of the authors read and approved the final version of the manuscript.


We studied acute and chronic pain in pediatric patients who underwent thoracotomy for benign disease with a follow-up of at least three months. A telephone interview investigated about the presence of pain and the analgesic therapy in progress. The results were compared with the anesthetic technique, postoperative pain and the adequacy of pain therapy, both during the first week after surgery and at the time of interview. Fifty-six families consented to the study. The mean age of the children at surgery was 2.9 ± 4.5 years, while at the time of the interview was 6.5 ± 4.4 years. We performed different anesthetic strategies: Group A: general anesthesia (36 pts); Group B: general anesthesia and thoracic epidural (10 pts); Group C: general anesthesia and intercostal nerve block (10 pts). During the immediate postoperative period, 21 patients (37.5%) had at least one painful episode. At the time of interview, 3 children (5.3%) had moderate chronic neuropathic (burning) pain on surgical scar. There was no statistically significant difference between the type of anesthesia and the incidence and severity of acute post-operative pain. Despite its limitations, this study confirms the low incidence of chronic post-thoracotomy pain syndrome in children. Thoracotomy is one of the most painful surgical procedures, not only in the immediate postoperative period, but also in the longer term after surgery . DespiteIn children, postoperative pain is often underestimated or misunderstood, both during hospitalization and, above all, at home ,10. The This study was aimed at evaluating the incidence of CPTPS in pediatric patients aged between 0 and 18 years old and at least 3 months after surgery.(1)The study included patients who underwent thoracotomy between 2007 and 2013 for benign diseases; children underwent a follow-up of at least three months and did not reach the age of majority (over 18 years old) in November 2013.(2)In June 2014, the families received a letter explaining the purpose and the method of the study and the request to collaborate. To prepare parents for the telephone interview, together with the letter a questionnaire for data collection, an informed consent was sent.(3)Fifteen days after the letters were sent, the telephone interview was performed. After establishing a positive contact, we asked them to return us via email, fax, or post the signed informed consent.(4)During the interview, we asked about the presence, type, intensity and location of the pain at the time of the interview and any analgesic therapy in progress.(5)Using the medical records referring to the period of hospitalization for surgery, we investigated the anesthetic technique used, the postoperative analgesic therapy prescribed and changes in pain during the first week of the postoperative period.(6)In the case of unsuccessful telephone contact, a second letter was sent as a reminder .This retrospective cross-sectional study has been approved by the Ethics Committee of Ospedale Pediatrico Bambino Gesù IRCCS on 06/11/2013 with number 957/RA and was articulated in the following way:Patients who reached the age of majority in November 2013, patients with malignant and inflammatory diseases, patients who did not have a follow-up of at least three months and patients of whom it was not possible to have an answer after the second letter of presentation were excluded from the study. Subjects removed from the study in case of non-response to the second letter, were not replaced.The prevalence of acute postoperative pain and the prevalence of chronic pain at the time of interview was investigated. The adequacy of pain treatment was assessed through the Pain Management Index (PMI) modified for the use on children . It compMoreover, with regard to the Neonatal Infant Pain Profile scale (NIPS) used for premature neonates under 32 weeks of age, scores of 0–2 indicate no pain and receive 0 points; scores of 3–4 indicate mild pain and receive 1 point; scores of 5–7 indicate severe pain and receive 3 points.Finally, the COMFORT scale provides a pain rating between 9 and 45 based on nine different parameters, each rated from 1 to 5. Scores of 9 indicates no pain and receive 0 points; 9–17 indicate no pain and receive 0 points; 18–26 indicate mild pain and received 1 point; 27–35 indicate moderate pain and receive 2 points; finally, scores of 36–45 indicate severe pain and receive 3 points. The COMFORT scale was used for sedated patients.PMI was computed by subtracting pain score from analgesic score. It ranges from −3 (patient with severe pain receiving no drug) to +3 (patient receiving strong opioids and reporting no pain); negative scores indicate undertreatment.The anesthetic technique used at the time of surgery was evaluated. Furthermore, postoperative pain and the adequacy of pain therapy, both during the first week after surgery and at the time of interview were evaluated ,14,15. PCategorical variables were summarized using absolute frequencies and percentages and continuous variables by the mean or median, as appropriate. To determine statistical differences between groups, we used the Chi-square test or Fischer’s exact test for categorical variables and the t-test or Mann–Whitney test for continuous variables.We performed comparisons of the three treatment groups with gender and median age in years  at surgery and treatment groups with median age in years  at interview. The results of the Chi-square test are not statistically significant.The sample size of 56 patients allows us to estimate the proportion of pain with an error of 13.1%, considering an alpha level = 0.05 and a confidence level of 95%. In this study, based on the estimate of the proportion of pain, we can rely on the measure of error of the estimate which is 13.1% considering a maximum variability (50%) which provides the most conservative estimate. The power of the study in this case cannot be detected as we do not have an effect size. Statistical analyses were carried out using the Stata program, version 13 .There were 172 eligible patients for the study with a 32.56% response rate: 56 patients were surveyed, 38 male, 18 female. There were no differences in age, gender and type of surgery between the surveyed group and the eligible group. The mean age of the children at the surgery was 2.9 ± 4.5 years, with a minimum of 0 and a maximum of 17.2 years, while the mean age of the children at the time of the interview was 4.4 ± 6.5 years with a minimum of 1 year and a maximum of 17.6 years. All patients underwent a thoracotomy to resolve their disease and they were divided into three groups based on their disease . We usedPostoperative pain therapy was performed mostly with intravenous morphine at a dose of 0.01 mg/kg/h or a continuous epidural with 0.125% ropivacaine at 0.1 mg/kg/h .The presence of postoperative pain and the efficacy of the administered therapy assessed using the hospital protocol are reported in Chronic postsurgical pediatric pain literature is sparse with many gaps on its precise pathophysiology ,16.In particular, the causes of post-thoracotomy pain, like chronic pain after surgery, are not well known. Female gender, psychological factors, genetic factors and nerve injury during surgery appear to play an important role in pre-and post-thoracotomy pain ,7,17,18.Few papers describe the incidence of acute postoperative pain in children. It can vary from 23% described by the Swedish authors to 70% on the 1st day, to 64% on the second day, with a progressive improvement up to 28% one week after the intervention described by American authors ,20. HoweLike Chou et al. , we founIn our study, the incidence of chronic post-thoracotomy pain we found is 5.3% (3 patients out of 56), a value of uncertain interpretation because there are few papers on this subject in pediatric age. These findings are positioned between 16% of 88 adult patients who underwent thoracotomy in childhood or youth as reported by Kristensen et al.  and accop-value for the chi-square test would be 0.05. Furthermore, the papers that investigate this particular type of pain in pediatric age are very few. Moreover, chronic pain is a very difficult field of research as the patient’s interview is almost always conducted by telephone and not in person. This fact jeopardizes the response of many patients, especially in the pediatric field, where the possible reasons can be many and of different nature. For example, reasons that can lead to non-response can be change of address, change of telephone number, conflict within the parental couple, death of the patient, disputes with the hospital, language barrier and technological barriers. Another reason is that in the pediatric field the case history is generally lower than that of adults. In addition, in this study we analyzed only non-oncological pathologies, precisely to avoid bias regarding oncological therapies and this further narrowed the search field.This study has several limitations. The main limitation is that the sample appears to be too small to draw firm conclusions. With a larger sample, the margin of error of the estimate would be reduced, for example by tripling the sample the error of the estimate is reduced to 7.6%. Consequently, with a tripled sample of 168 patients, maintaining the same proportions of pain obtained in the sample equal to 56, the In general, with regard to chronic pain in the pediatric field the request for micro-trials is becoming increasingly pressing, as the publication rate is low and first lines of evidence are needed to treat patients . ConsequApart the limited number of patients recruited, another limitation is the retrospective model and. Nevertheless, the paper is just a snapshot of our patients’ chronic pain because all the interviews were carried out at the same time and, therefore, at various intervals of time from each surgery.Despite its limitations, this study confirms the low incidence of chronic post-thoracotomy pain syndrome in children. Probably multi-year and multi-center prospective studies involving a larger number of patients are needed for obtaining more accurate data on the extent of the issue. Finally, other research is warranted to dissect the precise mechanism of postoperative chronic pain in the pediatric population.


Lumbar spinal stenosis (LSS) is a common degenerative condition associated with old age. Its incidence continues to increase with the rapidly aging population in China. Treatment for LSS usually begins with conservative treatments, as some patients refuse surgical procedures or have surgery contraindications. Caudal epidural steroid injections (CESIs) and selective nerve root blocks (SNRBs) are two commonly used conservative treatments for LSS, which have proven to be effective at relieving LSS symptoms in many studies. However, there are no randomized controlled trials comparing these two procedures. We planned the first study to assess which one of these two procedures is more effective in treating LSS. We will compare the efficacy of these two treatment methods in terms of duration of symptom relief and recurrence rate. We hope our findings will help clinicians choose an optimal treatment for LSS patients.We plan to conduct a 1-year randomized controlled trial that will include a total of 76 subjects. They will be randomly divided into two groups: group A (patients will receive CESIs) and group B (patients will receive SNRBs). Two days before the procedure, we will assess these patients using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale, Oswestry Disability Index (ODI), and numeric rating scale (NRS) for pain. One day, 2 weeks, 3 months, 6 months, and 1 year after the procedure, we will assess the condition of these patients again with the NRS and ODI.We hope our findings will lay the foundation for the design of further comprehensive studies and help clinicians make a choice between CESIs and SNRBs for LSS patients.ChiCTR1900028038. Registered on 8 December 2019Chinese Clinical Trial Registry  Lumbar spinal stenosis (LSS) is a lower back condition where the central canal, lateral recess, or neural foramina becomes narrowed. Common LSS symptoms are lower back pain, burning pain in the buttocks or legs, weakness, numbness or tingling, and loss of sensation . HoweverGiven that the causes of LSS tend to differ among different patients, doctors need to determine how and why a patient develops LSS in order to formulate a treatment plan that works best for him/her. The main pathogenesis of LSS is inflammatory changes around the nerve roots, congestion, and edema, which is also an important cause of root pain and the theoretical basis for corticosteroid injection to improve clinical symptoms –6. Ma etTo provide a scoring system that can guide LSS treatment and based on the pathogenesis and imaging characteristics of LSS, researchers have proposed the following grading system: grade 0—a normal intervertebral foramen; grade 1—mild foraminal stenosis with perineural fat obliteration in either the transverse or vertical direction; grade 2—moderate foraminal stenosis with perineural fat obliteration in both the transverse and vertical directions; and grade 3—severe foraminal stenosis with nerve root collapse or morphologic change , 10.Most patients seeking treatment for lower back pain have LSS. Treatments for LSS can be conservative and surgical. Conservative management is successful in most patients and is recommended as first-line treatment. Common conservative treatments for LSS include caudal epidural steroid injections (CESIs) and selective nerve root blocks (SNRBs). The reasons for their popularity among primary care physicians are as follows: First, compared with conventional surgical interventions, SNRBs and CESIs greatly reduce the time that physicians are exposed to X-rays, thus protecting their health. Second, SNRBs and CESIs are easy to perform and have a short learning curve.The efficacy of CESIs has been demonstrated in many studies. Delport et al. analyzed 140 patients treated with epidural steroid injection (ESI) . Fifty-tA selective nerve root block (SNRB) is a minimally invasive procedure; a needle is inserted into the epidural space in the foramen at the suspected spinal level, and medications such as steroids and local anesthetics are then injected into the area of a specific nerve root . This prNarrowing of the spinal canal caused by lumbar spine degeneration usually occurs slowly, over many years or decades. Substantial narrowing compresses the spinal nerves, which causes symptoms including pain at the early stage, and numbness and weakness of the extremities at the middle and late stages, severely affecting patients’ quality of life. Therefore, doctors should aim for early-stage interventions, offer effective treatments in the middle stage, and absolutely avoid late-stage surgery. In addition, it is recommended that patients in need of conservative treatments receive interventions as early as possible to prevent exacerbation of lumbar neuropathy.It follows from the above that both CESIs and SNRBs can effectively relieve clinical symptoms and improve neurologic function in patients with LSS. SNRBs are different from epidurals. Instead of administering medication to cover all the nerve roots, selective blocks are performed to target a particular pinched nerve root. SNRB injections can therefore be performed to manage a specific area of pathology without causing damage to nearby normal nerve tissues.To our knowledge, however, there have been no randomized controlled trials comparing the efficacy of SNRBs and CESIs. In clinical practice, primary care physicians often have to choose between a selective nerve block and a caudal epidural injection based on their own experience, as there is no guideline for them to refer to. To fill this gap, we plan to conduct the first study to compare the effects of SNRBs and CESIs on LSS. We will use outcome measures such as duration of symptom relief and recurrence rate to determine whether SNRBs or CESIs are more effective. We hope our findings will help physicians make a choice between SNRBs and CESIs for LSS patients.Our hypothesis is that SNRBs have a lower recurrence rate than CESIs in treating patients with single-level LSS.This is a randomized controlled trial, aimed at comparing the recurrence rate of LSS following treatment with SNRBs and CESIs in patients with one-level LSS. This study was approved by the Ethics Committee of the Fourth School of Clinical Medicine of Xinjiang Medical University and will be conducted in accordance with the World Medical Association Declaration of Helsinki. This study is registered in the Chinese Clinical Trial Registry (Registration No. ChiCTR1900028038). Written informed consent will be obtained from all patients before initiating treatment.Evaluation of the results and statistical analysis will be performed by professionals who are blinded to the group assignment. Participant flow is shown in Fig. The main outcome measures include the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale to determine whether the pain experienced is due to nerve damage, the Oswestry Disability Index (ODI) to assess functional status, and a numeric rating scale (NRS) for pain to evaluate pain intensity . Two dayFirst, we will assess the potential candidates and inform them of our study procedure. We will randomly divide the eligible patients into two groups after obtaining written informed consent from each patient. Treatment will be given to each patient based on the group he/she is in.n = 2(Zα + Zβ)2δ2/(D − Δ)2 . After we entered δ of 2.17, D of 0.1, and Δ of 1.2 into the formula, we found that it required 31 patients in each group. Given a loss to follow-up rate of 20%, approximately 76 subjects are required.Because the present study is a clinical application, according to the actual situation, it is difficult to calculate the sample size by pre-experiment, so we finally decided that the sample size of this study was obtained from the previous relevant literature data. The sample size outcome effect size is based on studies found in the literature using the ODI and NRS scores . The meaThis experiment was conducted simultaneously in the Second Spine Department of the Fourth School of Clinical Medicine of Xinjiang Medical University and Spine Department of the First Affiliated Hospital of Shihezi University, and inpatients meeting the inclusion criteria were included in the study.Since the LSS patient base of the above two departments is large enough to recruit subjects at the same time, there is no need to worry about the sample size. Some benefits can also be provided to patients participating in the study to supplement the sample size The inclusion criteria are shown in Table According to the “Clinical Guideline for the Diagnosis and Treatment of Degenerative Lumbar Spinal Stenosis by the North American Spine Society (NASS)” in 2011: Degenerative lumbar spinal stenosis describes a condition in which there is diminished space available for the neural and vascular elements in the lumbar spine secondary to degenerative changes in the spinal canal.The main clinical symptoms include sacroiliac joint pain and sharp radiating pain in the lateral thighs, lower legs, and feet, as well as lower extremity numbness and decreased muscle strength. Some patients also experience intermittent claudication. Leg pain and weakness are precipitated by walking or standing for a long time and relieved with forward flexion, sitting, and rest.2 (relative stenosis) and < 70 mm2 (absolute stenosis).Magnetic resonance imaging (MRI) represents the gold standard for the assessment of LSS: sagittal diameter of the lumbar central canal, 13–15 mm , 10–13 mm (narrow), and < 10 mm (absolute stenosis); dural sac area, < 100 mmDr. Jianhua Sun and Dr. Jing Li from the Spine Department of the First Affiliated Hospital, School of Medicine, Shihezi University, will use computer software to generate random sequences, which will be sealed in envelopes and concealed from recruiters and subjects. Ehsan from the Second Spine Department and investigator Akram are responsible for recruiting eligible patients. Zhenqiang Liu from the Second Spine Department will randomly assign recruited patients into two groups. In this study, we will use the single-blind approach in which the participant is unaware of which treatment he/she is receiving. The specific procedure performed will be kept hidden from all participants before unblinding.We also plan to charge all subjects the same fee to ensure the nature of blinding. The specific fees charged are as follows: nerve blocks 86 yuan + 2 vials of triamcinolone acetonide injection , 18.98 yuan + 1 vial of lidocaine , and 2.62 yuan + 1 vial of Omnipaque  (83 yuan). The total cost is 190.6 yuan.Patients will be randomly divided into two groups: group A (patients will receive CESIs) and group B (patients will receive SNRBs). Two days before the procedure, we will assess the condition of patients using the LANSS pain scale, ODI, and NRS for pain.The patient will be asked to lie in the prone position. A soft pillow approximately 10 mm thick is placed under the stomach area so that the sacrum is slightly elevated. The sacral hiatus is identified and marked on the skin. Following correct skin sterilization and draping, a surgeon will first practice inserting a 7-gauge spinal needle. A subjective feeling of “give” and loss of resistance suggests piercing the sacrococcygeal ligament.An 18-gauge spinal needle is then introduced into the anterior wall of the sacrum. Care is taken to ensure that the needle shaft is at an angle of 90° to the skin surface. Once the needle reaches the periosteum, it is tilted towards the caudal vertebra and advanced upward for up to 5 cm into the sacral canal with an angulation of 30° to the surface. The hub of the needle is then attached to the syringe. Loss of resistance when pushing air is characteristic of entering the sacral canal. After removal of the stylet and guidewire, and aspiration to check for blood or cerebrospinal fluid, 0.2–0.3 ml of Omnipaque is injected to confirm correct placement. If the contrast agent can be seen in the epidural space as confirmed by X-ray imaging, the needle is correctly placed. A mixture consisting of 80 mg of triamcinolone acetonide and 2 ml of 1% lidocaine is injected –24.The patient is placed in the prone position. The affected level is identified under C-arm guidance, and a horizontal line is marked at the level of the lower edge of the pedicle. After sterile preparation and draping, an 18-gauge spinal needle is inserted 0.5 cm below the marked line and 10 cm from the spinous process at an angle of 25–30° to the coronal plane and parallel to the intervertebral space on the axial plane. For local anesthesia, 1% lidocaine is injected when advancing the needle. Under C-arm guidance, the direction and depth of the needle are observed, and it is inserted where the nerve root exits. Anteroposterior and lateral X-ray imaging of the lumbar spine is performed again when inserting the needle through the intervertebral foramen. On the anterior-posterior view, the tip of the needle is placed approximately 0.5 cm beneath the corresponding pedicle. On the lateral view, the needle tip is positioned just below the pedicle and into 1/3 of the posterior aspect of the intervertebral foramen. Radiating pain along the nerve occurs if the nerve root is punctured. The patient is asked whether this is the site he/she experienced pain. Then, 0.2 to 0.3 ml of Omnipaque is injected into the nerve root sheath to clearly visualize the existing nerve root. When an adequate flow of contrast medium to the target area occurs, a solution consisting of 80 mg of triamcinolone acetonide and 2 ml of 1% lidocaine is injected .We will evaluate the treatment outcomes using the NRS and ODI 1 day, 2 weeks, 3 months, 6 months, and 1 year after the procedure. The treatment plan and evaluation of results are shown in Table Multiple outcome measures were utilized which included the NRS  pain scale and the ODI on a 0–50 scale, with assessment at 1 day, 2 weeks, 3 months, 6 months, and 1 year after the procedure. The Oswestry Disability Index (ODI): back pain-related dysfunction will be assessed using the ODI. The ODI contains 10 questions about daily activities, including inventories of pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sexual life, social life, and traveling. Each question is rated on a scale from 0 to 5 points; the lower the score, the less disabled the person is by the pain. The NRS represented no pain with a 0 and the worst pain imaginable with a 10. NRS is an instrument for the self-assessment of pain and comprises a scale with 0 and 10 at either end of a straight line. The participants marked a point on the line to indicate their level of average pain. The value and validity of the NRS and ODI have been reported , 29. TheDuring the 1-year follow-up period, we will use paper case report forms and self-reported questionnaires to collect data. All data collection will be supervised in strict accordance with the standard procedure of the clinical trial center to ensure full compliance with International Council for Harmonization (ICH) standards and Good Clinical Practice (GCP) principles. Any patient who experiences adverse events such as worsening of clinical symptoms and loss of ability to perform daily activities during the study period will be fully evaluated by doctors’ inquiries, physical examination, and imaging studies. If the adverse event is believed to be caused by the intervention received, the treatment will be terminated and the patient will be offered symptomatic treatment. We will analyze relevant data on adverse events and LSS interventions to improve treatment. All adverse events will also be reported to the investigators. Given the short period and low risk of our study, we did not set up a Trial Steering Committee. Any unexpected events will be directly reported to the investigators for advice. There is no interim analysis was set in this protocol, and WH and AO will have access to decide whether to make the final decision to terminate the trial.For the control group and the experimental group, other treatments allowed for the patients are as follows: (1) both groups can be given routine nursing treatment in Department II of Spine of Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region, including daily inquiry of patients’ condition, pain improvement, and care for patients. (2) Acupuncture and moxibustion treatment of lumbar spinal stenosis was performed by a doctor designated by the Acupuncture and Moxibustion Department of the said hospital. Standardized acupuncture and moxibustion treatment of lumbar spinal stenosis was adopted, that is, acupuncture and moxibustion treatment was the same for all subjects. (3) The massage treatment of lumbar spinal stenosis was performed by the designated physician in the Department of Massage of the said hospital. The standardized treatment of lumbar spinal stenosis with acupuncture and massage was used, that is, all subjects had the same massage treatment. (4) The treatment can be performed by the designated nurse of Department II of Spine and ensure that all subjects are electrically treated in the same position. The other treatments allowed are traditional Chinese medicine treatment, which can play the role of adjuvant treatment, and the two groups of patients received the same treatment. As a result, the effect of the above treatment on the experimental results can be avoided. For the control group and experimental group, the other treatments prohibited from the patients are as follows: (1) In the course of the experiment, other invasive treatments for lumbar spinal stenosis were performed, (2) It is forbidden for the subjects to take drugs that can improve the clinical symptoms of lumbar spinal stenosis. (3) Patients were not allowed to receive other treatments for lumbar spinal stenosis without the consent of the researcher. (4) They took related analgesics by themselves.Xiao Luo, a physician of Spine Department II, had an informed conversation with the subjects 2 days before the operation and obtained consent from the subjects. After Dr. Luo Xiao obtained the informed consent from the subjects, Nianrong Han, a physician of Spine Department II, asked the subjects for the basic information and related medical history of the patients required for the experiment, which was also completed 2 days before the operation. Ehsan Abduhani, a physician of Spine Department II, checked whether the subjects met the prescribed criteria 1 day before the operation and finally determined whether they were included in the experiment. Researcher Akram Osman completed his work of LANSS scoring 2 days before the operation after Dr. Luo Xiao and Dr. Han Nianrong completed their work. After then, Akram Osman and Zhengqing Liu completed the follow-up collection of ODI and NRS. It should be noted that for the same subject, the same person should always follow up and collect data, which cannot be carried out alternately. The follow-up collection of data must be completed within 24 h on the specified date. Akram Osman is responsible for sorting and inputting the collected data into the designated data collection table and setting the password to save independently. This work is completed within 24 h after receiving the data.All patients have the right to drop out of the study at any time. If a patient chooses to discontinue participation, we will withdraw consent from this patient and terminate the study. The chief investigator can also terminate a subject’s participation if he/she breaks the rules governing this study or has severe adverse events. Data on these subjects will be excluded from our final analysis.Two investigators will use EpiData 3.0 for data entry. SPSS18.0 will be used to analyze all data. All patients’ demographic and clinical characteristics  will be subject to descriptive analysis. Quantitative data will be expressed as mean ± standard deviation, medians, and ranges, while qualitative data will be expressed as frequency and percentage. A chi-squared test will be used to compare the incidence of adverse events between patients in the two groups.The study results will be published in relevant medical journals. The chief investigator together with the members of the research management team and other investigators will write the manuscript and submit it to a journal for publication.Both SNRBs and CESIs have proven efficacy against LSS. However, there are no studies comparing the effectiveness of these two treatments in LSS. In clinical practice, primary care physicians often have to choose between these two procedures based on their own experience as there is no guideline for them to refer to. Such subjectivity raises the risk of adopting a suboptimal treatment plan for a patient, which can result in less than desirable outcomes and increase the uncertainty surrounding the prognosis of patients. In severe cases, treatment can fail, increasing patients’ pain and economic burden. To avoid patients receiving inappropriate treatment, we evaluated the effects of SNRB and CESI treatment for LSS. We will divide recruited LSS patients into two groups and offer them either SNRBs or CESIs. Data including duration of symptom relief and time to relapse in patients in the two groups will be recorded, and the recurrence rate will be calculated to determine whether SNRBs or CESIs are more effective in relieving patients’ symptoms long term. We hope our findings will provide a reference for physicians and help them make a choice between SNRBs and CESIs for LSS patients based on scientific and clinical evidence so that these patients can receive optimal treatment with maximal efficacy.The version number of this protocol is no. 3.0, date: 2020-1-28. The date of subject start recruitment is 2020-4-16, and we expect to complete all research processes by the end of 2021.


Introduction: Chronic pelvic pain is a highly prevalent pain condition among women, but identifying the exact cause of pelvic pain remains a significant diagnostic challenge. In this study, we explored a new diagnostic approach with PET/MRI of the sigma-1 receptor, a chaperone protein modulating ion channels for activating nociceptive processes.Methods: Our approach is implemented by a simultaneous PET/MRI scan with a novel radioligand [18F]FTC-146, which is highly specific to the sigma-1 receptor. We recruited 5 chronic pelvic pain patients and 5 healthy volunteers and compared our PET/MRI findings between these two groups.Results: All five patients showed abnormally increased radioligand uptake on PET compared to healthy controls at various organs, including the uterus, vagina, pelvic bowel, gluteus maximus muscle, and liver. However, on MRI, only 2 patients showed abnormalities that could be potentially associated with the pain symptoms. For a subset of patients, the association of pain and the abnormally increased radioligand uptake was further validated by successful pain relief outcomes following surgery or trigger point injections to the identified abnormalities.Conclusion: In this preliminary study, sigma-1 receptor PET/MRI demonstrated potential for identifying abnormalities associated with chronic pelvic pain. Future studies will need to correlate samples with imaging findings to further validate the correlation between S1R distribution and pathologies of chronic pelvic pain.Trial Registration: The clinical trial registration date is June 2, 2018, and the registration number of the study is NCT03195270 . Chronic pelvic pain is a common, debilitating medical condition affecting approximately 15% of women in westernized countries with rates ranging from 6 to 27% worldwide . While tThe most common gynecologic causes of chronic pelvic pain in women include endometriosis, prior pelvic inflammatory disease, ovarian cysts, adhesions, adenomyosis, and leiomyoma. Other etiologies include urologic, gastrointestinal, musculoskeletal, and neurologic conditions . ComprehMagnetic resonance imaging (MRI) is currently the non-invasive imaging modality of choice for many of the causes of pelvic pain, particularly for those of musculoskeletal and neurologic origin, and, as such, MRI is increasingly being used for gynecological evaluation. However, MRI is generally tailored toward a certain diagnosis or pathology, and the most common source of pelvic pain in women, endometriosis and adhesions, can be still challenging to identify on MRI. Prior studies have shown that MRI has high specificity but low sensitivity for detecting these pathologies, and up to 46% of patients with chronic pelvic pain that have no findings on MRI are found to have a gynecological structural cause on laparoscopy  or have Sigma-1 receptors (S1Rs) are a unique class of intercellular chaperone proteins widely distributed throughout the whole body , 13. Inchttps://clinicaltrials.gov/ct2/show/NCT03556137).This prospective observational study was approved by the Stanford University Institutional Review Board, and all subjects signed a written informed consent form prior to imaging experiments. All data were collected in compliance with the Health Insurance Portability and Accountability Act. The clinical trial registration date is June 2, 2018, and the registration number of the study is NCT03195270 (Five patients with chronic pelvic pain (age range 25–69) under the care of our OB/GYN surgeon (DL) and five healthy female controls (age range 28–49) were recruited. All patient subjects had had pelvic pain in the past 6 months at the time of referral to our study. To qualify for the study, patients had to report an average pain level of 4 or higher on a 0–10 visual analog scale (VAS)  on the dBoth patient and control participants fasted for 4 h before the PET/MRI scan and were injected with 10 mCi of [18F]FTC-146 via the antecubital vein in a bolus injection. 30 min after the injection, the simultaneous PET/MRI scan that covers the whole body in 8–10 bed positions was acquired using a hybrid GE SIGNA PET/MRI scanner . A combination of a head/neck coil, two anterior body array coils, and a spine coil was used for the signal reception. The following MRI sequences were performed for each bed position: 3D axial fast spoiled gradient-recalled echo with 2-point Dixon for fat-water separation (LAVA-FLEX) and 2D axial T2-weighted fast-spin-echo with triple-echo Dixon for fat-water separation (T2-FLEX). In the bed position for imaging the pelvis, we additionally adopted the following MRI sequences from the standard non-contrast pelvic MRI protocol in our clinical sites: 2D axial T1-weighted fast spin-echo sequence (T1-FSE), 2D axial T2-weighted fast spin-echo sequence with fat saturation (T2-FS-FSE), 2D sagittal T2-weighted PROPELLER sequence (T2-PROPELLER) , and 3D Images were first reviewed independently by two radiologists (AF and SB) with at least 5 years of experience in reading pelvic MRIs, including looking for adhesions and endometriosis, to identify S1R-PET/MR abnormalities in comparison to healthy control subjects. The diagnostic pelvic MR images were first reviewed to identify pathology that could be contributing to the patient's pelvic pain symptoms. The PET images in the unit of standardized uptake value (SUV) were subsequently reviewed to look for marked abnormal uptake in comparison to the imaging pattern of the controls. The co-registered PET and MRI images were then reviewed using the patient surveys regarding the location and laterality of pain at the time of imaging. After the first review, radiologists consulted each other about PET/MRI findings, and they became congruent in the end.max) of [18F]FTC-146 was measured for each segmented region of individual control subjects. For each region, the mean and standard deviation of SUVmax across the five controls was calculated to evaluate the SUVmax of identified local hotspots of [18F]FTC-146 uptake from patients. The z-score of SUVmax for the identified hotspot was computed as max of the hotspot, and u and δ are the mean and standard deviation of SUVmax from the associated control organs among the 5 segmented types above. Image segmentation and SUV measurement were performed manually by the radiologists using Horos (https://horosproject.org/). The image findings were later matched to the follow-up treatment outcomes for validation, if available at the time of the image analysis.The pelvic region was segmented into 5 organ types  and the maximum SUV  except for those of increased vaginal uptake from Patient 3 and liver uptake from Patient 2. The z-scores of SUVmax from all patient and control subjects are plotted in In all five patient participants, abnormalities with increased uptake of our S1R radioligand were identified during the image review as summarized in max of 9.5) around the fibroid, which did not take up the tracer. The fibroid had been also shown to not enhance on previously performed clinical pelvic MRI with contrast. max of 5.8. She previously underwent a laparoscopic hysterectomy and bilateral salpingo-oophorectomy for presumed endometriosis, however, her pathology only showed adenomyosis and India ink. Our imaging findings are hypothesized to potentially reflect underlying adhesive disease or an underlying bowel pathology. max of 5.5) was observed, as compared to the healthy controls. Note that this patient also presented increased uptake in the uterus and pelvic bowel, fitting the suspected multifactorial causes of the symptom including endometriosis and adhesions.No adverse event was identified during the post-imaging monitoring period. Patient 1 underwent a laparoscopic hysterectomy with pathology showing an infarcted fibroid and endometriosis in the bilateral pelvic sidewalls, left uterosacral ligament, and uterine serosa. These features would correlate with stage 2 endometriosis. A hysterectomy successfully resolved her pelvic pain, reducing the pain intensity from the VAS score of 8/10 before the surgery to the VAS score of 0/10 at the post-operative exam. Patient 3 ultimately underwent a diagnostic laparoscopy, cystoscopy, and vaginal trigger point injection. She was found to have one lesion of endometriosis in the left pelvic sidewall, which was excised and confirmed to be endometriosis on pathology. The finding was consistent with stage 1 endometriosis. Fortunately, her pain did improve post-operatively.In this work, we presented the preliminary results of our S1R PET/MRI study on chronic pelvic pain patients. To our knowledge, this is the first study to demonstrate the feasibility of using S1R PET/MRI to identify potential pelvic pain generators. S1R has been previously reported to be upregulated on tissues under painful conditions to activate ion channels for pain-signaling. The purpose of our study is to investigate if our S1R PET/MRI may find differences between chronic pelvic pain patients and healthy controls, which might be used to locate pain generators. In our preliminary results, S1R PET images showed abnormalities that were likely associated with the pain symptom in all 5 patients while MRI showed potential abnormalities in only 2 of the 5 patients. Abnormally increased signal on S1R PET images was observed in different organs including the uterus, pelvic muscle, pelvic bowel, vagina, and liver compared to those of healthy controls. Our findings demonstrate that the proposed S1R PET/MRI approach can be used to examine the correlation of S1R and pelvic pain in a variety of pelvic organs.MRI has been widely used when pelvic ultrasonography findings are unclear or when the spread of deep pelvic endometriosis should be assessed for presurgical planning , 26. It The pelvic MRI protocol in our study is composed to closely match the standard non-contrast pelvic MRI protocol adopted in the clinical sites of our institution. Though the sample size is limited, our result suggests that S1R PET may help revealing abnormalities that were previously undetected or very difficult to detect with MRI. Therefore, the proposed joint imaging approach of S1R PET and MRI may provide a more comprehensive and inclusive evaluation given the vast possible etiologies for pelvic pain. One of the most striking findings from our current work is the intense amount of uptake around the bowel in women who previously had extensive lysis of adhesions (Patient 2) and/or stage 4 endometriosis (Patient 5). Both of these entities are typically challenging to identify on MR imaging alone, and the adhesive disease tends to be a diagnosis of exclusion. Prior population studies have shown that between 50 and 61% of all women with pelvic pain lack a clear diagnosis , 27, andThere are a several limitations and future directions for this study. This is a small sample size with a variety of potential diagnoses, which limited the adoption of more rigorous statistical tests for the measurements and inter/intra-observer variabilities. The study of a larger control and patient cohort will be followed to conduct a randomized controlled trial to mitigate any potential bias in our case-control study format. Recruiting larger numbers of patients with known diagnoses would also help to validate the findings, and one goal is to recruit several patients with known diagnoses, such as endometriosis, adenomyosis, and fibroids, to see what the uptake patterns are for these diagnoses. The comparison with contrast-enhanced MRI scans , 29 willIn conclusion, our early results demonstrate the potential use of S1R PET/MR in diagnosing pain generators in chronic pelvic pain. Given the many possible etiologies of chronic pelvic pain and the fact that many patients have more than one cause of their pain, this novel approach could help locate/distinguish specific pain generators and guide treatment based on molecular and structural findings. This molecular imaging of the sigma-1 receptor may also help identify conditions that are currently challenging to diagnose with the standard of care structural imaging, such as adhesive disease or distant endometrial implants, and guide/evaluate treatment, which would greatly benefit these patients.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Institutional Review Board of Stanford University. The patients/participants provided their written informed consent to participate in this study.DL and SB: conceptualization, study design, and supervision. DY, PC, BS, JC, and CM: data acquisitions. AF, DY, and SB: drafting of the manuscript. SB and CRM: funding acquisition. All authors: formal analysis, investigation, and reviewing and editing.General Electric Healthcare provided research funding to DY, PC, and SB. This work was also supported by the University of Florida Clinical and Translational Science Institute, which was supported in part by the NIH National Center for Advancing Translational Sciences under award number UL1TR001427 (CRM).DY, PC, and SB received research support from General Electric Healthcare. The remaining 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.


Background. Pain is one of the main aspects of hidradenitis suppurativa that strongly affects the quality of life of patients. We explored the relationship between pain and clinical severity as well as its role in defining the health status in patients with HS. Methods. Pain was defined by three measures: (a) question 1 (“my skin hurts”) of the Skindex-17; (b) Bodily Pain (BP) scale of the SF-36; and (c) Visual Analog Scale (VAS). Clinical severity of HS was assessed by the Hurley staging, the Sartorius HS Score, and the International HS Severity Score System. Results. The study population included 341 HS patients with complete data for the VAS pain, 316 for question 1 of the Skindex-17, and 294 for BP. Clinical severity was positively associated with pain. This result was observed for all three severity scores and all three pain evaluation methods. In addition, the number of fistulae, abscesses, and nodules were significantly associated with the three severity measures of pain, while the association with scars was not observed for question 1 of the Skindex-17 and BP. Conclusions. Pain may be a good proxy of clinical severity and efficacy of a treatment in HS and therefore a crucial hallmark of patients’ health status. Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory skin condition characterized by abscesses in the apocrine gland-bearing areas of the body . Data onDue to recurrent flares, sinus tracts, abscesses, fistulas, and scarring, HS is an extremely painful condition . The 199A large European case-control multicenter study showed pain to be the highest in patients with HS among several other dermatological conditions ,14. AddiIt is reasonable to assume that pain may be strongly associated with clinical severity as measured by the classical severity indexes, such as Hurley staging, Sartorius score, or IHS4.Our hypothesis was that pain may be a good proxy for the evaluation of clinical severity in HS and that even a simple measurement, such as a VAS scale, may provide useful, comprehensive information.The purpose of this study was thus to explore the relationship between pain and clinical severity as well as its role in defining the state of health in HS patients by using different pain measures.This is a cross-sectional, observational study on patients with HS conducted in a research hospital. The study has been approved by the Institutional Ethical Committee of IDI-IRCCS, Rome, Italy (protocol number 608-1).Consecutive patients with HS were recruited between August 2016 and October 2019 at the dedicated HS outpatient clinic of IDI-IRCSS, a national dermatological reference center in Rome, Italy.Patients aged 16 years or more; with a new diagnosis of HS or presenting for the first time to the hospital; with a history of at least 6 months of nodules, abscesses, fistulae, and secondary retracting scars; affected intertriginous sites; and who signed an informed consent were included in the study.Patients unable to understand the Italian language or the questions or those with major psychiatric conditions were excluded.1.Question 1 of the Skindex-17The Skindex-17  measures2.Bodily Pain (BP) scale of the SF-36Pain was also evaluated using the BP scale of the SF-36, which is a generic indicator of health status . The BP 3.Visual Analog Scale (VAS) of painPain during the previous week was also evaluated using a VAS from 0 (no pain) to 10 (worst imaginable pain).Clinical severity of HS was assessed by the Hurley staging , the SarMean scores of the three clinical severity measures  were compared in different levels of pain scores using one-way ANOVA.Question 1 of the Skindex-17 was analyzed according to the original scoring . BP was categorized as <25, 25–49, and 50 or higher. VAS pain was categorized as <5, 5–6, or ≥7. Additionally, the different components of severity, i.e., mean number of fistulae, abscesses, nodules, and scars, were compared according to the level of pain.Tukey’s post-hoc test was used for pairwise comparisons. Mean SF-36 scale scores were graphically represented according to the different levels of pain. For question 1 of the Skindex-17, two groups were created: one experiencing pain never/rarely/sometimes and the other often/always. Mean values were compared using Mann-Whitney U test.All analyses were performed using IBM SPSS Statistics for Windows, Release 26.0.0.1 .The study population included 341 HS patients with complete data for the VAS pain, 316 for question 1 of the Skindex-17, and 294 for the BP scale of the SF-36. There were 131 males (38.4%) in the first group, 127 (40.2%) in the second group, and 111 (37.8%) in the third group. Mean age (standard deviation) was 32.4 (11.9), 33.3 (11.6), and 32.6 (11.7) years, respectively.Severity was significantly, positively associated with pain .This result was observed for all severity and pain measures. As to the different components of clinical severity, the number of fistulae, abscesses, and nodules were significantly associated with the three severity measures of pain. On the contrary, the association with scars was not observed for two out of the three pain scales . The comparison of subgroups by pairs showed that, in general, differences were significant between the group with the highest level of pain and each of the other groups.Mean values of the 8 scales of the SF-36 are graphically represented in In In this study, we reported a very strong association between pain and clinical severity measures in patients with HS. This result was observed for all three severity scores and all three pain evaluation methods we used. The issue of pain in skin diseases is noteworthy, and its diagnosis and treatment are an important aspect in the management of the diseases. HS-related pain may be acute or chronic . Acute pPain is reported by a large majority of patients with HS. For example, in the study by Matusiak et al. , 77.5% oA more recent and extensive study of 1795 HS patients  showed tPain is thus a crucial component of quality-of-life impairment in HS even more than disease severity . It has In research and particularly in clinical trials, it is important to measure outcomes, such as pain, to evaluate the efficacy of a treatment or to study the natural history of the disease. Some studies on pain in HS have used specific instruments . The advThe strong association observed in the present study between pain and clinical severity corroborates our hypothesis that pain may be a good proxy for the evaluation of clinical severity in HS. Information on pain may be easily obtained by a simple measurement, such as a VAS scale, or a question extrapolated from a questionnaire. The fact that the patient may be considered as an expert in the evaluation of her/his own disease severity has been confirmed by research data. It has been shown that patient self-assessments of flare activity and pain are strongly associated with morphological changes identified using ultrasound . TherefoIn conclusion, pain is a crucial hallmark of HS and an essential factor in defining health status of patients. It should be a privileged therapeutic target in patients suffering from this chronic and sometimes disabling dermatosis. Moreover, changes in pain severity may be a good proxy measure of the efficacy of a treatment.


Although intravesical botulinum toxin type A (BoNT-A) injection for functional bladder disorders is effective, the injection-related problems—such as bladder pain and urinary tract infection—make the procedure invasive and inconvenient. Several vehicles have recently been developed to deliver BoNT-A without injection, thereby making the treatment less or non-invasive. Laboratory evidence revealed that liposome can carry BoNT-A across the uroepithelium and act on sub-urothelial nerve endings. A randomized placebo controlled study revealed that intravesical administration of liposome-encapsulated BoNT-A and TC-3 hydrogel embedded BoNT-A can improve urinary frequency, urgency, and reduce incontinence in patients with overactive bladders. A single-arm prospective study also revealed that intravesical administration of TC-3 hydrogel embedded BoNT-A can relieve bladder pain in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We recently administered suprapubic energy shock wave (ESW) after BoNT-A intravesical administration in six patients with IC/BPS. Although pain reduction and symptom improvement were not significant, immunochemical staining showed cleaved synaptosome-associated protein 25 in the bladder after the procedure. This suggests that ESW can promote passage of BoNT-A across the uroepithelium. In conclusion, using vehicles to intra-vesically deliver BoNT-A for functional bladder disorders is promising. Further studies are necessary to confirm the efficacy and explore novel applications. In summAll patients tolerated the procedure well without any complications; however, the therapeutic effect was not significant. Reduction of pain on the visual analog scale, and symptoms score in Interstitial Cystitis Symptom Index and Problem Index, were not significantly improved in this pilot study with six patients . Two of We summarized current clinical evidence of non-invasive intravesical BoNT-A delivery for patients with functional bladder disorders in the Using vehicles to intra-vesically deliver BoNT-A for functional bladder disorders is promising. Further studies are necessary to confirm the efficacy and explore novel applications.


A cause of groin pain after total hip arthroplasty (THA) is mechanical irritation or impingement of the iliopsoas tendon. The incidence is about 4%. If conservative therapy fails, an arthroscopic release of the iliopsoas tendon can be performed. The aim of the study was to assess the mid-term clinical outcome after arthroscopic release. We hypothesize that good results can be achieved by a minimally invasive endoscopic procedure.Using our in-house database, all patients who received an endoscopic release of the iliopsoas tendon due to mechanical irritation after THA were identified. Inclusion criteria were mechanical irritation of the iliopsoas tendon after cementless THA with minimal acetabular component prominence. Exclusion criteria were marked prominence of the acetabular component and groin pain after THA for any other reason. In these patients, the modified Harris Hip Score (mHHS), the pain level using the numerical analogue scale and the UCLA Activity Score were measured. The mean follow-up period was 7 ± 3.8 (2.6–11.7) years.p = 0.001). The pain level on the NAS decreased significantly from 8.5 ± 1.2 (7–10) to 2.5 ± 1.8 (0–6) points (p = 0.001). The activity level based on the UCLA Activity Score raised from 4.0 ± 2.7 (0–7) to 6.5 ± 1.8 (3–9) (p = 0.09).25 patients were identified in whom an arthroscopic release of the iliopsoas tendon had been performed since 2007. The data of 20 patients were available at follow-up. The gender ratio was 1:1, the average age at the time of arthroscopy was 59 ± 27.7 (52–78) years. The average interval between THA and arthroscopy was 6.3 ± 4.0 (1.7–15) years. The mHHS showed a significant improvement from preoperative 31.2 ± 9.8 (17.6–47.3) to 82.0 ± 9.8 (46.2–100) points (Mechanical irritation and impingement of the iliopsoas tendon is an important diagnosis to be considered in persistent groin pain after total hip arthroplasty. In failure of non-operative treatment, good clinical results can be achieved with arthroscopic release and the pain level can be significantly reduced.IV. The majority of patients after total hip arthroplasty (THA) are very satisfied with the result achieved . HoweverTypically, these patients complain of pain in the groin area , 12. ActFirst and foremost, conservative therapy as the gold standard should be attempted. This includes physical therapy, peritendinous injections or non-steroidal anti-inflammatory drugs (NSAIDs) , 19, 20.Regarding the outcome, most studies report a short follow-up period averaging 8 months to 3 years , 24, 28.This is a single-center retrospective cohort study. After institutional review board approval (Ethikkommission Landesärztekammer Baden-Württemberg: F-2019-006), we identified patients via our institutional database in July 2019 and performed a retrospective analysis of prospectively collected data. We included patients that had undergone primary cementless total hip arthroplasty and subsequently sustained iliopsoas impingement. All surgeries were performed by the senior author.Diagnosis was founded on clinical and imaging evidence that was based on AP-pelvic and cross-lateral radiographs and computed tomography Fig. . In addiThe surgical procedure is performed under general anesthesia in the supine position using a traction table and a perineal post. The hip is prepared and draped in the usual fashion. Two standard portals are used for each arthroscopy and established under the use of fluoroscopy . The 70° arthroscope is inserted through the proximal anterior portal and a radiofrequency device through the midanterior portal. First scar tissue is dissected until the head and socket are identified. Then a capsulotomy is performed at the iliopsoas notch. After identifying the iliopsoas tendon, it is released at the impingement zone using a radiofrequency device or a shaver Fig. .Fig. 2LeFor the first 2 weeks, hip flexion is pain-dependent permitted and the patient can be mobilized pain-adapted to crutches. Physical therapy starts on the first postoperative day. After 2 weeks, the crutches are discontinued and physical therapy should focus on strengthening the gluteus medius and core muscles, as well as progression of range of motion.t test. Categorical variables were tested using the Fisher exact test. To determine whether there are preoperative patient characteristics that may have some influence on the outcome a Spearman’s correlation analysis was conducted. Variables used in the analysis were age, gender, BMI, smoking status, and symptom duration in month before surgery. A p value of less than 0.05 was considered to be statistically significant.Statistical analyses were performed using SPSS Statistics 24 . Continuous variables were compared using unpaired Student’s 2. Mean interval between THA and arthroscopy was 6.3 ± 4.0 (1.7–15) years. The gender ratio was 1:1 . All patients were treated with a cementless cup and a cementless stem. The laterality showed twelve right and eight left hips. The patients included had direct lateral (13 patients) or dorsal surgical approach (7 patients). None of the patients had an anterior approach. Radiological analysis showed correct cup inclination (40°–50°) in 16 patients (80%). In four patients (20%), the cup was found to be more vertical (> 50°). Two patients had an anteversion of the acetabular component of < 10°. The mean prominence of the acetabular component was 5.5 ± 1.8 (2–8) mm.Between January 2007 and December 2016, a total of 25 patients received arthroscopic release of the iliopsoas tendon. Of these 25 patients, 2 had died in the meantime, 2 had moved and were lost to follow-up and 1 refused to participate. Data of 20 patients were available at mean follow-up of 7 ± 3.8 (2.6–11.7) years. Mean age at arthroscopy was 59 ± 27.7 (52–78) years. Mean BMI was 25.7 ± 5.5 (20.4–34.5) kg/mBefore hip arthroscopy each patient reported pain with hip flexion, five patients complained of occasional snapping. The ability to flex was painfully limited in all patients; however, active flexion against resistance was possible without any weakness. Pain location was 95% inguinal, 40% thigh and 25% adductors.p = 0.0001). UCLA activity score showed an improvement but without statistical significance (p = 0.09)  of patients had a resolution of pain, 2 patients still reported some residual symptoms, but these were markedly less than preoperative. All five patients with occasional snapping did not complain of any further snapping phenomena. Modified Harris Hips Score and VAS pain showed significant improvements at follow-up  and VAS pain . Age, gender, smoking status, and duration of symptoms had no influence on the results.The correlation analysis showed that BMI had a significant influence on the improvement achieved in mHHS and VAS pain: a higher BMI was significantly associated with a higher improvement in mHHS  Harris Hip Scores are over 90 points . One reaThe current study has some limitations. First it is a retrospective study. The included group was small with 20 patients. However, most published studies reported smaller groups with 6–10 patients , 24. JerOne of the main strengths of our study is the long follow-up time of 7 years. To our knowledge, our study has the longest follow-up period. Another strength of the study is that all operations were performed by one surgeon (W.M.).Mechanical irritation and impingement of the iliopsoas tendon is a differential diagnosis to be considered in persistent groin pain after total hip arthroplasty. Patients show typical symptoms such as painful active flexion of the hip. The therapy of choice is initially conservative. However, with frustrating conservative therapy, good clinical results can be achieved with arthroscopic release and the pain level can be significantly reduced with a very low complication rate. The endoscopic release, therefore, represents a minimally invasive alternative to acetabular component revision.


This systematic review and meta-analysis aimed to synthesize the evidence on the effects of psychosocial interventions on pain in advanced cancer patients.d = − 0.29, CI = − 0.54 to − 0.05). Effect sizes were highly heterogeneous between studies. We did not find evidence for the superiority of any of the intervention types. However, psychosocial interventions may be more effective if they specifically targeted pain distress as the primary outcome.The included studies investigated the effects of relaxation techniques, cognitive-behavioral therapy, music therapy, mindfulness- and acceptance-based interventions, and supportive-expressive group therapy. Overall, we found a small, but significant effect on pain intensity (Although findings were mixed, psychosocial interventions can be recommended to complement comprehensive care to alleviate pain in patients facing an advanced or terminal stage of the disease. Future research should develop innovative interventions tailored specifically for pain relief. Pain is prevalent in 50.7% of cancer patients . In advaNot only does the biopsychosocial model predict maladaptive processes, but also it provides potential psychological and social resources for dealing with cancer and the accompanying pain condition. The physical sensation of pain can strongly be shaped by the individual’s psychological appraisal . Hence, When it comes to social resources, support from close persons can be a major factor . HoweverBased on the perspective of biopsychosocial integration, a wide array of non-pharmacological interventions is available to cancer patients nowadays. Evidence-based approaches encompass physical treatments like massage and gymnastics, educational interventions with respect to illness and treatment, and psychosocial interventions. The latter can play an important role in improving the quality of life of patients, especially in advanced cancer stages or palliative care where physical activity is strongly limited. Psychosocial interventions specifically address feelings, thoughts, and behavior , includiGenerally, psychosocial interventions have a beneficial effect on the quality of life and other psychological health outcomes in cancer patients across all stages of the disease , 14. In Furthermore, only some of these studies assessed pain as a primary or secondary outcome. Meta-analyses revealed small, but significant effects of psychosocial interventions on pain severity and pain interference in various stages of the disease , and forEven fewer research studied patient populations in advanced and terminal cancer stages •. CognitDuring the fluent transition to palliative and end-of-life care settings, effective pain management can be a crucial determinant of cancer patients’ quality of life , 3. ConsTo summarize the latest evidence on the abovementioned research topic, we conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . MoreoveInclusion criteria were defined according to the PICOS framework  . The revA systematic search was conducted using the electronic databases PubMed, PsycINFO, and CINAHL. We combined search terms describing psychosocial interventions  with those targeting at palliative care/advanced cancer, at clinical trials , and at pain. The complete search syntax can be sent on request by the corresponding author. In addition to the electronic search, the reference lists of the selected studies and similar systematic reviews were hand-searched. The search was conducted in June 2019.n = 376) and hand-search (n = 3) into Rayyan, an online tool for systematic reviews [n = 209). Conflicting assessments were resolved by discussion between the two raters. A total of 182 records were excluded because they did not meet the criteria with regard to publication type (n = 67), study design (n = 68), population (n = 22), intervention (n = 18) or outcome (n = 5), or no full-text access (n = 2). Complete full texts of the remaining studies (n = 27) were then screened. Of those, 13 were excluded because they did not meet the criteria regarding publication type (n = 3), study design (n = 1), population (n = 3), intervention (n = 2), or outcome (n = 4). Finally, 14 articles were included in the narrative synthesis. In order to perform a quantitative synthesis, authors were contacted via e-mail asking for data that was not reported, but necessary for the calculations. Three articles were excluded because the data could not be obtained. Eleven articles were included in the quantitative synthesis. We then extracted basic characteristics together with information on patients, interventions, study designs, outcomes, and statistical results according to a predefined data coding sheet.We entered records identified through database  [Standardized mean change differences for pretest-posttest-control-group designs were calculated following the method described by Morris . In orded > 0.8) .Q- and I2-statistics. Moderator analyses were conducted to determine the following possible sources of heterogeneity: type of setting , type of intervention , number of sessions, total duration of the intervention, type of control , and as pain primary vs. secondary outcome. Type-I error probability was set at α = 0.05.For further meta-analytic calculations, we used the metafor package in R . HeterogThe following section is a narrative synthesis of information from primary studies, categorized for different intervention approaches. Table Guided relaxation appears to be effective in the treatment of pain , 36 whilWhile the aforementioned studies explored the effects of live guided relaxation, Kwekkeboom et al. examined the efficacy of self-administered mp3-recorded exercises consisting of relaxation, imagery, and distraction techniques. In a pilot study  and a fuAnother self-administered relaxation technique is electromyography (EMG) biofeedback–assisted relaxation which Tsai et al. investigated in patients with advanced cancer . In 6 seAlthough the search terms aimed at a variety of creative arts–based approaches , only studies regarding music therapy fit the criteria. Other creative arts–based therapies such as dance and movement therapy may not be applicable in palliative settings. The results are inconclusive with some studies providing evidence for music therapy as effective for pain treatment , 40 and In contrast, Warth et al. found no differences in pain perception between the intervention and control groups . PalliatCognitive-behavioral interventions can also support pain relief in cancer care. The EASE study by Rodin et al. examined the efficacy of a combination of psychotherapy and physical symptom screening on pain, other symptoms, and quality of life in patients with acute leukemia ••. Over Acceptance and commitment therapy (ACT) aims at increasing present-moment awareness and psychological flexibility through mindfulness and behavior-change strategies. Therefore, the interference of unwanted internal experiences, like pain, may also be decreased. Mosher et al. examined the efficacy of acceptance and commitment therapy in patients with metastatic breast cancer . PatientTwo studies with the same design showed that supportive-expressive group therapy in combination with hypnosis reduces the increase of pain experience in patients with metastatic breast cancer over a time period of 1 year , 47. Patd = − 0.35  and significant heterogeneity among the individual effects . Figure Eleven studies were included in the quantitative synthesis. All of them provided data on pain intensity and three additionally reported data on pain interference. A random effects model revealed a small, but statistically significant reduction of pain intensity with a pooled effect of d = − 0.29, CI = − 0.54 to − 0.05). None of the tested moderators could significantly help to explain variance between primary effect sizes . However, the distinction between studies that specifically targeted pain as the primary outcome and those who did not, revealed a statistic trend (p = 0.09). This finding suggests that pain-specific psychosocial treatments may lead to greater pain reductions (d = − 0.44) than interventions that primarily aimed at different constructs, such as depression, quality of life, or general symptom distress (d = − 0.17).Visual inspection of the individual effects revealed one possible outlier  with a pd = − 0.28, CI = − 1.69 to 1.12, p = 0.48). The overall effect is presumably heterogeneous, but because of the small number of individual effects, no further analyses were performed.Regarding pain interference, the pooled effect was weak and not statistically significant  in the statistical analyses, as only four studies implemented and reported follow-up data assessments. Hence, no conclusions about long-term effects of psychosocial interventions can be drawn from this overview.The present review shows that psychosocial interventions, in general, can have a beneficial effect on self-rated pain severity of advanced cancer patients. Thus, psychosocial interventions can be recommended to complement state-of-the-art medical pain control. Adverse effects are rarely reported, and psychosocial cancer care may additionally have a preventive effect on other common symptoms, including fatigue, depression, and anxiety. While the magnitude of effects did not vary for different intervention types, we identified relaxation-based techniques, music therapy, cognitive-behavioral therapy, and supportive-expressive group therapies as promising. However, findings for all intervention types were mixed and more research is needed on techniques that are specifically designed to target pain symptoms.


Pain is a common symptom of acromegaly, impairing health-related quality of life (HR-QoL) significantly despite long-term disease remission. Neuropathic-like pain (NP-like) symptoms are invalidating, with great impact on HR-QoL. Studies characterizing or investigating the etiology of pain in acromegaly are scarce. Therefore, we aimed to assess NP-like symptoms in a cohort of controlled acromegaly patients.Forty-four long-term controlled acromegaly patients  were included in this cross-sectional study. NP-like symptoms were assessed using the validated painDETECT questionnaire. Patients were divided in three probability-based NP-like symptoms categories based on the total score (range 0–35): unlikely (≤ 12), indeterminate (13–18) and likely (≥ 19). HR-QoL , and mental component score (MCS)), and self-reported pain were assessed using Short Form-36 (SF-36). Potential risk factors were determined using linear regression analyses.Self-reported pain was reported by 35 patients (79.5%). Likely NP-like symptoms were present in 4/44 patients (9.1%), and indeterminate NP-like symptoms in 6/44 patients (13.6%). All patients with likely NP-like symptoms were female. Higher painDETECT scores were negatively associated with HR-QoL , and SF-36 pain scores . Female sex was a risk factor for NP-like symptoms.Pain was prevalent in controlled acromegaly patients, whereas NP-like symptoms were relatively infrequent, and only observed in females. NP-like symptoms were associated with lower HR-QoL in acromegaly. Since specific analgesic therapy is available, awareness for characterization, increased understanding, and clinical trials regarding neuropathic pain identification and treatment in acromegaly patients are warranted.The online version contains supplementary material available at 10.1007/s11102-021-01190-z. Acromegaly is associated with an abundance of partially irreversible symptoms and comorbidities, significantly contributing to decreased health-related quality of life (HR-QoL) , which iincl. compression neuropathies) [Considering the diverse etiology of pain in acromegaly patients, the origin, and type of pain are difficult to determine. Generally, pain can be divided into two types: nociceptive pain caused by activation of nociceptors, and neuropathic pain resulting from lesions/diseases of the peripheral somatosensory nervous system . Neuropapathies) , 19–21. pathies) , 23.To our knowledge, only one previous study investigated neuropathic pain in pituitary adenoma patients, including acromegaly, of whom 20% reported neuropathic-like pain symptoms . In the All patients gave informed consent for this cross-sectional observational study, which was approved by the Medical Ethics Committee. A standardized questionnaire on medical history, and current health condition was completed, including the past and current use of medication. Serum samples were obtained to assess pituitary function. Validated questionnaires, including a specific neuropathic pain symptom questionnaire, were filled out (vide infra).Forty-four patients with well-controlled acromegaly with complete neuropathic pain questionnaires were included in the present study. Twenty-five patients in remission that participated in our long-term follow-up study on musculoskeletal acromegalic complications  werClinical assessment of patients with acromegaly has been described previously , 25–31. Serum GH levels were measured using a nationally harmonized assay  . For IGFPatients filled out all questionnaires based on their health status at the moment of the study visit. Notably, because of the observational nature of the study, the current prescribed treatments, and medications were continued.painDETECT Questionnaire (painDETECT) was validated to identify neuropathic-like pain symptoms in various conditions including lower back pain, rheumatoid arthritis, and primary OA [The 9-item imary OA –41. The imary OA . Based oimary OA , 44. OutAdditionally, information on pain localization was extracted from the drawings of individual patients on the human figure within the painDETECT questionnaire. Data were available for 31 patients. Pain localization was divided into 4 categories: (1) pain in one specific location, (2) pain in one limb, (3) pain in two separate limbs, and (4) pain diffusely spread throughout the body  to measure hand disability [Disabilities of the Arm, Shoulder and Hand (DASH) to assess disability of the upper limb [Western Ontario and McMaster Universities Arthritis Index (WOMAC) to evaluate lower limb joint symptoms [All patients completed the following questionnaires: sability ; Disabilper limb –48; Westsymptoms , 49. In symptoms —used forsymptoms –48, 50—usymptoms —used to Short Form-36 (SF-36) [Patients completed the HR-QoL questionnaire  (SF-36) . Physica (SF-36) , with hi (SF-36) . Based oSPSS for Windows version 25.0  was used for data analysis. Data are presented as N (%), mean ± SD, or median (IQR). Pearson’s correlation analyses and linear regression analysis using numerical 7-item painDETECT total scores were performed. P-values < 0.05 were considered significant.Forty-four patients with controlled acromegaly  were included, as summarized in Table Pain was reported by 35 patients (79.5%), and median SF-36 pain component scores were 68.4 (IQR 57.1–89.8). Pain medication was used by 12 patients . Median painDETECT total scores were 5 (IQR 2–12), as shown in Table . diabetes mellitus, polyneuropathy, carpal tunnel syndrome, brachial plexopathy, disc herniation, neural foraminal stenosis, spinal cord injury). When assessing whether the locations of pain from these comorbidities overlapped with the regions of pain indicated on the painDETECT questionnaire, overlap of the painful regions was observed in four patients , whereas no overlap was observed in three patients.Three of four likely-NP patients suffered from relevant comorbidities: demyelinating polyneuropathy (N = 1), diabetes mellitus (N = 1), and spondylolisthesis (N = 1). Of the six patients with indeterminate neuropathic-like pain symptoms, two patients suffered from a disc herniation, one patient had diabetes mellitus, and one patient had multiple sclerosis. Twelve unlikely-NP patients suffered from relevant comorbidities , amitriptyline prescribed for neuropathic pain caused by demyelinating polyneuropathy), and two indeterminate-NP patients (SSRIs prescribed for depression (N = 2)).Higher painDETECT scores were correlated with lower HR-QoL , especially with the pain component scores , as depicted in Fig. . surgery and radiotherapy vs pharmacological treatment) , active disease duration , remission duration , or hypopituitarism .The effects of age, sex and BMI, all being factors known to influence neuropathic pain in the general population , were asRadiation of pain could be assessed in 37 patients Table . RadiatiIn addition, 31 patients provided drawings to assess pain localization. None of the patients reported pain in one limb (category 2), whereas examples of the other categories are shown in Fig. The present explorative, questionnaire-based study reported that, despite a high prevalence of pain in controlled acromegaly patients, neuropathic-like pain symptoms are a relatively infrequent finding, and occurred in females only. Patients with higher painDETECT scores, reflecting a higher probability of neuropathic-like pain symptoms, reported lower HR-QoL, and more OA-related disability. All but two patients with likely or indeterminate neuropathic-like pain symptoms were diagnosed with relevant comorbidities. Apart from female sex, no other  factors were associated with neuropathic-like pain symptoms in our cohort.vs 5.7% in males), and individuals > 50 years of age [Neuropathic pain is caused by altered sensory signal transduction to the brain due to lesions or diseases of the somatosensory nervous system. Symptoms typically include burning, tingling sensations (dysesthesia), and pain upon non-painful stimuli  . In the s of age , which ss of age , 57.In the present study, some form of pain was self-reported by over 75% of patients with controlled acromegaly, which is in line with previously reported prevalence . HoweverFurthermore, we assessed the localization of pain, and presence of pain radiation. The localization of pain was limited to one specific location or joint in 25% of patients, with 75% patients localizing their pain in multiple limbs and joints, or present diffusely throughout the entire body. Furthermore, radiating pain—a phenomenon whereby pain of one specific origin is perceived in other locations—was observed in approximately 40% of patients. Since radiating pain is one of the characteristics of neuropathic pain, presence of pain radiation might underline the existence of, or risk to develop neuropathic pain in the future.Higher upper and lower limb disability scores, and lower mental and physical HR-QoL were observed in patients with  neuropathic-like pain symptoms. These observations are in line with general population studies showing that neuropathic pain is generally more invalidating than nociceptive pain , 18, andBased on the findings of our study, and the scarcely available literature on neuropathic pain in the general population, we have constructed an algorithm for the diagnostics and management of pain in acromegaly, summarized in Fig. Several limitations need to be addressed. Notably, outcomes of the SF-36 pain component and painDETECT questionnaire were partially non-overlapping, resulting in a potential higher prevalence of pain of over 85% in the present population. Moreover, as the study cohort was small, numerical questionnaire outcomes were used for analyses, whereas the painDETECT questionnaire was originally developed to have a categorical outcome. Additionally, presence of neuropathic-like pain symptoms was solely determined based on the painDETECT questionnaire, as clear, objective criteria for identifying neuropathic pain remain unavailable. Furthermore, the origin of neuropathic pain in acromegaly is difficult to determine, as multiple painful complications may coexist. Lastly, the present patient population included controlled acromegaly patients only, whereas patients with active disease might be more severely affected with regards to neuropathic (pain) symptoms.In conclusion, although pain is a prevalent symptom in acromegaly patients, the infrequently occurring neuropathic-like pain symptoms—only found in females—suggests that pain in controlled acromegaly mostly is of nociceptive nature. The presence of neuropathic-like pain symptoms was associated with lower mental and physical HR-QoL and more OA-related disability. We advise to assess for neuropathic-like pain symptoms in patients with compromised HR-QoL, and severe, persisting pain despite regular pain medication.Supplementary file1 (PDF 141 kb)Below is the link to the electronic supplementary material.