Total knee arthroplasty (TKA) is considered an effective treatment for pain relief and improved physical performances in end-stage knee osteoarthritis. However, several studies have reported less favorable outcomes after TKA with chronic pain rates of approximately 20%. Exercise might be an effective treatment strategy for chronic pain following TKA, but no randomized controlled trials have evaluated its effect. Therefore, the purpose of this randomized controlled trial is to investigate whether a 12-week neuromuscular exercise  program combined with pain neuroscience education (PNE) provides greater pain relief and improvement in physical performances than PNE alone at 12 months follow-up in a population of patients with chronic pain after primary TKA.4 (KOOS4), defined as the mean score for the KOOS subscales pain, symptoms, activities of daily living, and quality of life. Secondary outcomes include all KOOS subscale scores and scores for PainDETECT, the Fear-Avoidance Beliefs Questionnaire, Global Perceived Effect, the Pain Catastrophizing Scale, pain intensities, temporal summation, conditioned pain modulation, and pressure pain thresholds. Physical performances are measured with walking, stair climbing, and chair standing tests as well as tests of muscle strength and power.For this randomized controlled superiority trial, 120 patients with moderate-to-severe chronic pain after TKA are recruited from Aalborg University Hospital, Denmark. Patients are randomly assigned in a 1:1 ratio to one of two interventions: (a) NEMEX-TJR twice weekly for 12 weeks combined with two sessions of PNE or (b) two sessions of PNE given over 6 weeks. Assessment is performed at baseline before intervention and at 3, 6, and 12 months after initiation of the intervention. Outcome assessors are blinded toward group allocation. The primary outcome is the change in the Knee Injury and Osteoarthritis Outcome ScoreThe findings will be useful in establishing effective treatment strategies for chronic pain after TKA. The randomized controlled trial involves rigorous scientific methods and uses clinically applicable interventions. The study interventions are conducted in clinical settings, thereby enhancing the possibility of future implementation of the treatments in the health care systems.NCT03886259. Registered 22 March 2019. Ethics committee registration: N-20180046.ClinicalTrials.gov identifier:  Osteoarthritis (OA) is considered the most frequent cause of disability and pain in the elderly population, and the knee joint is one of the joints most commonly affected , 2. End-A systematic review reported that 20% of patients felt that TKA surgery had not been successful enough to resume their regular activities of daily living (ADL), including walking, stair climbing, dressing, and getting in and out of bed . TherefoGuidelines for knee OA have established exercise as an effective treatment for both pain and functional impairment , 11. ForA neuromuscular exercise  program developed by Ageberg et al. (2010) has been shown to be feasible and effective in treating pain and impaired function in patients with end-stage knee OA and immediately following TKA surgery , 15. TheOver the last few years, a shift in patient information from the biomedical model to a biopsychosocial model has been proposed as education for chronic pain patients , 18. SinWe initiated the NEPNEP (Neuromuscular Exercises and Pain Neuroscience Education for chronic Pain) trial with the purpose of evaluating whether a 12-week NEMEX-TJR program combined with PNE provides greater pain relief and improvement in physical performances than PNE alone in a population of patients with chronic pain after primary TKA. We hypothesize that NEMEX-TJR and PNE in combination can provide greater pain relief and better physical performance compared to PNE alone after 12 months.This study is a randomized controlled superiority trial with blinding of both the outcome assessor and the statistician analyzing the data. This study protocol follows the recommendations of the SPIRIT  guideline  see sup. In conjhttps://clinicaltrials.gov/ct2/show/NCT03886259). Any changes to the trial protocol will be communicated to the ethics committee and the clinical trial registry. All patients will be thoroughly informed about the trial before inclusion and will sign informed consent forms before participation. The NEMEX-TJR program used in the current trial has been found to be feasible and safe to use  of 15)  of 15) . A two-sThe patients will be randomized in a 1:1 ratio to one of two treatment arms: (1) NEMEX-TJR and PNE or (2) PNE alone. Using computer-generated random numbers in permuted blocks of four to eight patients, the project manager will randomly assign patients to either of the treatment arms after the informed consent has been signed and the baseline assessment conducted.Patients will participate in the interventions at the local Departments of Occupational and Physiotherapy in the northern region of Denmark. These departments are part of the Aalborg University Hospital, Denmark.Patients in the exercise and PNE group will receive a 12-week rehabilitation program consisting of the NEMEX-TJR program . The NEMBoth treatments groups will receive the same PNE consisting of two group-based educational sessions: one at the start of the trial period and one 6 weeks after the initiation of the trial. Both sessions will take 1 hour and be conducted by a physiotherapist trained in PNE. The sessions cover topics concerning the multifactorial nature of chronic pain, sensitization, hyperalgesia, allodynia, and plasticity of the brain, aiming at giving patients a better understanding of their chronic pain and thereby engaging the patients in the treatment. Information leaflets summing up the PNE topics will be handed out to the patients after the PNE sessions. During the sessions, it will be possible to ask questions and share experiences within the patient group.Baseline measurements will be completed prior to randomization and follow-up measurements will be conducted at 3, 6, and 12 months after initiation of the intervention. All assessment will take place at the Department of Occupational and Physiotherapy, Aalborg University Hospital, Denmark  to 100 (best) [The primary outcome will be the change from baseline to 12 months in KOOS0 (best) . A minim0 (best) .Several patient-reported outcome measures will be collected Fig. . The sco2 probe will be used to record the pressure pain threshold (PPT) in kPa, which can be reliably assessed using pressure algometry [2 with a frequency of 1/s. Then, the patients will rate the intensity of the last stimulus on an NRS. Dynamic mechanical allodynia will be examined using a cotton swab stroked four times on the skin (twice from each direction of a cross with 90° angles). The length of each stroke will be 3–5 cm. The patients will rate the pain intensity induced by the stroke on an NRS. Deep somatic hyperalgesia will be measured using a bedside pressure algometer (syringe). The air in the syringe will be compressed at a constant speed (1 ml/s) until the pressure becomes painful. The patients will be asked to indicate when the pressure became painful (threshold in ml). Pressure pain thresholds and bedside tests for sensitization will be recorded in the area of the index knee, adjacent to the knee , and extra-segmentally on the medial side of the forearm . Conditioned pain modulation will be assessed using PPT as test stimuli and a spring-based pressure clamp applying a force of 1.3 kg as conditioning stimuli. Test stimuli will be applied to the middle part of the tibialis anterior muscle of the non-affected side and conditioning stimuli will be applied to the ipsilateral earlobe. The patients will be asked to report their use of pain medication during last week (yes/no), including the number of paracetamols (1 g), ibuprofen (400 mg), and other nonsteroidal anti-inflammatory drugs.Pain intensity ratings will be measured using NRS for the average daily pain intensity over the last week prior to the visit and the maximal pain intensity during rest (day and night), walking, and stair climbing. Patients will also be asked to draw their habitual pain distribution on anatomical body maps . A handhlgometry , 36. TheFive objective physical performance measures will be collected Fig. . Based oAdverse events that may occurr during the trial period will be identified by the patients (self-reported) and by the physiotherapists supervising the interventions (observations). Adverse events are characterized as occurring in the index knee or sites other than the index knee and serious events are defined according to the definitions from the U.S. Food and Drug Administration . Non-ser2 test, Fisher exact test, or a Mann-Whitney U test as appropriate. A per-protocol analysis will be performed for the primary outcome, excluding patients who had poor adherence to the intervention, defined as participating in less than 75% of the exercise sessions and not attending both PNE sessions, and excluding patients who undergo additional surgery during follow-up. A 95% confidence interval (CI) excluding 10 points or more in the KOOS4 score will be interpreted as a lack of a clinically meaningful difference between groups. P values and 95% CIs will be presented. All authors will have access to the final anonymized trial dataset.The statistical analysis of the primary outcome will be performed according to an intention-to-treat principle. Statistical tests will be dependent of data distribution. We expect data to be normally distributed, and therefore, aim at using a repeated measures mixed model with patients as random effect and time  and treatment arm  as fixed effects, and with adjustments for baseline imbalance. No imputation will take place. Secondary outcomes and other endpoints will be analyzed similarly to the primary outcome. The frequency of adverse events will be compared between groups at the 12-month follow-up using a Poisson regression model with robust error variance. Categorical outcomes will be analyzed using a ΧSee title page for members of the trial steering committee. All members participated in the conception of the study design and procured funding. The principal investigator (JBL) is coordinating the ongoing trial. The trial steering committee reviews the progress of the trial and agrees the necessary changes in the protocol, if any.All obtained results will be collected using a test score protocol or fulfilling questionnaires and thereafter, entered into Excel . From Excel, data will be transferred into SPSS version 25.0  for statistical analyses. All collected test score protocols and questionnaires will be kept in a locked place as back up. Anonymized study data in electronically format will be stored at an encrypted network. Access to study data is restricted and cannot be accessed without permission.The North Denmark Region Committee on Health Research Ethics selects a number of approved studies for audit every year. These audits are independent from the trial steering committee and possible study sponsors.Results will be published regardless of outcome. Authorship will be determined based on the guidelines from the International Committee of Medical Journal Editors. The authors do not have any publication restrictions.The aim of this trial is to evaluate the effects of a treatment that could potentially relieve pain and improve physical performance as well as provide education to assist patients in handling their chronic pain and disability. This is of definite importance since no other randomized controlled trial has been conducted regarding exercise as treatment for chronic pain after TKA , 13. TheThe strengths of the trial are the use of rigorous methods that include randomized allocation, blinding of outcome assessors, and the use of clinical applicable interventions. The trial interventions are conducted in clinical settings, thereby enhancing potential future implementation of the treatments in health care systems.There are some potential limitations of the trial. Since the patients have chronic pain, some may use pain medication. This could interfere with the assessment of pain. In order to reduce possible bias from this, the use and dosage of medication will be assessed, allowing the study group to evaluate whether the use of pain medication increased or declined during the trial. Chronic pain patients often have comorbidities or other painful musculoskeletal disorders  that mayThe trial is ongoing and is currently recruiting patients. Recruitment was initiated on April 12, 2019 and is expected to be completed by the end of December 2021. This protocol is based on protocol version 4.0 of the 16 August 2018. The trial was registered with ClinicalTrials.gov (NCT03886259) on the 22 March 2019.Additional file 1. SPIRIT 2013 Checklist for the NEPNEP trial.Additional file 2. The TIDieR (Template for Intervention Description and Replication) Checklist for the NEPNEP trial.


Cervical radiculopathy is usually caused by disc herniation or spondylosis. The prognosis is expected to be good in most patients, but there is limited scientific evidence on the indications for nonsurgical and surgical treatments. The aim of the present study is to evaluate and compare the effectiveness of surgical and nonsurgical treatment in two trials – including disc herniation and spondylosis, respectively, and to evaluate factors that contribute to better decision making.Patients with disabling radicular arm pain and MRI-proven cervical disc herniation or spondylosis will be randomised to receive nonsurgical or surgical treatment. The follow-up period is one year and the sample size is estimated to be 50 for each arm in the two trials, giving a total of 200 patients. The primary outcomes are the Neck Disability Index and arm pain. Secondary outcomes include neck pain; EQ-5D and costs to evaluate cost-effectiveness; prognostic factors; CT and MRI scans, to estimate intervertebral foraminal area and nerve root compression; and the expected minimal improvement for willingness to undergo treatment.The outcomes of this study will contribute to better decision making in the treatment of cervical radiculopathy.NCT03674619, on September 17, 2018.This study has been registered at ClinicalTrials.gov as  Neck pain is among the leading causes of disability worldwide . The yeaIn contrast, the yearly prevalence of cervical radiculopathy is relatively low. It was estimated to 83/100000, peaking in fourth and fifth decades, in a large epidemiological study applying wide criteria, including neck and arm pain, and corresponding MRI findings indicating that one or more nerve roots were affected . CervicaCervical disc herniation and spondylosis may trigger local ischemia and inflammation, mediated by biochemical and immunological factors that contribute to the pathophysiology of radiculopathy . High leThe natural course of cervical radiculopathy is difficult to outline. Recent studies have described a favourable course at an average of 6 months, with complete recovery ranging from 24 to 36 months , 9. TherThe most common surgical treatment is discectomy and fusion . AnterioThe success rates of surgical interventions are reported to range between 80 and 95% ; howeverThere is limited knowledge on the indications for surgery in patients with pain syndromes in general, and particularly in patients with cervical radiculopathy caused by disc herniation. It is believed that the prognosis of non-operative treatment is better in patients with disc herniation than in patients with spondylosis, but there is a lack of clinical trials to corroborate this. One reason for this is that a strict classification based on MRI-findings has been difficult to obtain. Surgery is conducted to decompress the nerve root, but the correlation between the intervertebral foraminal area, root compression, and symptoms has been poorly investigated, and findings are questionable because neither the measurement error nor the inter-rater agreement of findings has been reported. Albert et al. found no postoperative correlation between surgical graft height and symptom relief . The intFurther research may improve our understanding and reverse or limit current practice. Forty-two per cent of practices believed to be effective, were reversed according to a systematic review evaluating trials published in a high impact journal over a 10-year period . For exaThe current study aims to evaluate the effectiveness of surgical and nonsurgical treatment in two separate trials on patients with disc herniation and spondylosis, respectively. The trials will be merged to evaluate cost-effectiveness, prognostic factors, radiology, and expected outcome. The studies are likely to contribute to better evidence for the treatment of cervical radiculopathy.The primary aim of this study is to compare the effectiveness of surgical and nonsurgical treatment in patients with cervical radiculopathy through two separate trials, one including disc herniation and the other including spondylosis Fig. . SecondaTo test the hypothesis that the effectiveness of surgery measured by the mean difference in Neck Disability Index (NDI) and arm pain – adjusted for the baseline at a 1-year follow-up – in patients with cervical radiculopathy does not differ from nonsurgical treatment in:Study 1: one-level disc herniation (C5/6 or C6/7)Study 2: one- or two-level spondylosis (C5/6 and/or C6/7)2.To test the hypothesis that surgery is more effective in patients with more clinical findings  at the baseline.3.To estimate the cost-effectiveness for healthcare costs and societal costs (including sickness absence) in surgical versus nonsurgical patients.4.To assess radiological (MRI and CT) measurements of the foraminal area and nerve compression, and whether morphological changes at the 1-year mark can predict clinical changes (NDI and arm pain).5.To evaluate treatment-outcome expectations by asking patients to fill in their expected improvements at the baseline, and to compare these with previously published MCIC values and outcomes at the 1-year mark.This study is designed as two randomised controlled trials comparing cervical decompression and non-operative treatment with cost-effectiveness analysis and the assessment of expectations and predictors of outcomes. The main research question will be evaluated through a one-year follow-up. The trial is registered with the Norwegian ethics committee, REK 2017/2125, and in Clinical Trials – as NCT03674619 – on September 17, 2018. The trial follows the recommendations put forth by SPIRIT  .All patients referred to Oslo University Hospital for treatment of cervical radiculopathy – from levels C5/C6 and C6/C7 – will be screened for inclusion in the study. The patients are primarily referred by their general practitioners, private clinics, or neurology departments at other hospitals in the Health Region South-Eastern Norway, covering a population of about 2.9 million inhabitants.This definition of cervical radiculopathy is according to a previously described minimum criteria set . The incThe patients will be informed about the study in detail, both through a standardised written text and orally. They will be informed about what is already known, including the natural course and the effectiveness of the two interventions.Patients with any previous cervical fractures or cervical spine surgery; signs of myelopathy; rapidly progressive paresis or paresis < grade 4; pregnancy; arthritis involving the cervical spine; infection or active cancer; generalised pain syndrome; serious psychiatric or somatic disease that excludes one of the treatment alternatives; concomitant shoulder disorders that may interfere with the outcome; abuse of medication/narcotics; inability to understand written Norwegian; and unwillingness to accept one of the treatment alternatives.The patients will be randomized using Viedoc electronic randomisation. This is an independent institution that uses permuted blocks that are unknown to the patient coordinator, which will randomise patients in study A and B. The randomisation process is unknown to the patient coordinator, who is not involved in treatment and evaluation. The coordinator will accordingly make treatment appointments.The outcome assessor and the statistician will be blinded to treatment allocation. The data will be extracted in an unidentifiable manner and will not contain any information that can reveal what treatment a single subject or a group were randomised to.All the interventions will commence within 2–3 weeks after randomisation.A recent systematic review that included 39 randomised controlled trials concluded that the surgeon, patient, and healthcare provider can choose any surgical technique based on experience, preference, and cost . In the Anterior discectomy will be performed, and a microscope will be used. After separation of the platysma muscle, the pre-vertebral space is reached by an approach medial to the sternocleido-mastoid muscle and carotid artery, and lateral to the trachea and oesophagus. Subsequently, the disc is incised and the corpora are distracted to perform discectomy. Usually, the posterior ligament is cut, the spinal root is decompressed, and – if necessary – the arthritic rims are removed. An inter-vertebral fusion device then is inserted. Two levels are allowed in the spondylosis study.Patients will first meet an experienced specialist in physical medicine and rehabilitation, who will answer their concerns and questions, and repeat the information given before inclusion, if necessary. The aim of this brief intervention is to promote a better understanding and coping with the condition. The intervention will further include supervision by a physiotherapist , who will provide advice on how to handle secondary neck muscle pain and dysfunction, reduce eventual fear behaviour, and provide advice to stay active.Study subjects randomised to nonsurgical intervention will have the option of crossing over to surgery. They will simply have to express their wish to cross over to the treating physician or physiotherapist. The expected reasons for cross overs are a rapid decline in the neurological status or unbearable pain in the arm. The surgeon will then conduct a new assessment and, after a short observation period, these patients will be offered the option of surgery.Baseline data will be obtained before randomisation and 12, 26, and 52 weeks after randomisation.The primary outcomes are:The Neck Disability Index, which consists of ten questions about pain-related disability, including items such as headaches, concentration problems, reading issues and sleep disturbances. Each item is rated by choosing one of five response categories, and then transformed into a total score ranging from 0 to 100 (worst possible). The Norwegian version has been validated in patients with neck pain and with cervical radiculopathy , 35.Arm pain, measured by a Numeric Rating Scale (NRS) from 0 (no pain) to 10 (worst imaginable pain) .Follow-up at 52 weeks is the primary endpoint.The secondary outcomes are:Neck pain, measured by a Numeric Rating Scale (NRS) from 0 (no pain) to 10 (worst imaginable pain).Perceived recovery or change of the main symptoms, rated on a numeric scale ranging from − 9 (worst possible change) to 9 (best possible change) .EuroQol (EQ-5D and EQ-VAS). EQ-5D includes five facets: mobility, self-care, daily activities, pain/discomfort, and anxiety/depression, and each has three response categories. The responses are transformed into and indexed to value the patients’ health-related quality of life for a cost–utility analysis. Patients score their health from 0 (as bad as possible) to 100 (best possible) by EQ-VAS. The Norwegian version has been validated in patients with back pain, idiopathic scoliosis, and cervical radiculopathy , 38, 39.Fear-avoidance beliefs, evaluated using the Fear Avoidance Beliefs Questionnaire (FABQ) –43.Emotional distress will be assessed by the 10-question version of the Hopkins Symptom Check List (HSCL-10) , 45.Medicine consumption the week before inclusion and the week before each follow-up will be registered.Sickness absence data will be collected from the National Social Security Institution for the year before and after inclusion.Dysphagia .Frequency of complications .Frequency of reoperation after surgery and frequency of operations in patients allocated to nonsurgical treatment.Other treatments. We will register concomitant care and interventions. There are no restrictions related to concomitant care.Exploring global success rates by asking the patients about how their arm and neck pain are compared to prior to treatment (ranging from much worse to much better).Patient expectations. Exploring patient expectations ahead of treatment. The patients are asked to fill out the Neck Disability Index – as if they were at 52 weeks post-treatment – and selecting the lowest category they would be content with for each item. The patients are also asked to report what they expect their symptoms to be like in 52 weeks (ranging from much worse to much better), registered for arm pain, neck pain, and headaches separately.Outcomes of the predictor and cost–utility analyses are briefly outlined in Tables Outcomes of the radiology study and the expected-outcome study are briefly outlined in Table The timing of the outcome measurements is outlined in Table p < 0.05) in NDI at a 1-year follow-up of 12, assuming a standard deviation of 18. Assuming a 10% drop-out and 20% cross-over rate, we plan to include 50 patients in each group in each trial, giving a total of 200 patients for evaluation of predictors.Including 36 patients in each treatment group is estimated to have 80% power for detecting a clinically significant difference . Sensitivity analyses, including those with treatments performed according to the protocol, will be added. A non-parametric bootstrapping technique will be used for health economic analyses. Kappa and limits of agreement will be estimated, and logistic and linear regression will be applied to analyse radiology. Predictors will be analysed using multiple-linear and logistic regression. The expected primary outcomes will be calculated for each patient; mean values (95% CI) will be estimated.The project will involve all the departments  treating patients with cervical radiculopathy at Oslo University Hospital (OUS). Because the population covered by OUS is about 2.9 million, we have decided to conduct the study at OUS and not involve other neurosurgical institutions in Norway. All referrals will be coordinated from the respective units, and possible candidates for inclusion will be evaluated by a specialist in physical medicine and rehabilitation , along with an experienced neurosurgeon . Only patients with cervical radiculopathy will be included in the study. Neck pain itself, even accompanied by radiological findings, is not an indication for surgery. A research nurse will handle patients found to be eligible after oral and written consent is obtained. The study group consists of experienced researchers who have expertise in conducting large, high-quality, randomised controlled trials. Surgeries will be performed by an experienced neurosurgeon and non-operative treatment by an experienced specialist in physical medicine and rehabilitation. The head of physiotherapy, along with physiotherapists who are currently conducting non-operative treatments of these patients at the physical medicine and rehabilitation department, have been engaged in the planning and running of the non-operative treatment. Two study secretaries at the neurosurgical department have coordinated another RCT at the department with great success, which is of importance for the quality of the current project.Patients included in the planned trial are all surgical candidates with high expectations for surgery. The physicians recruiting the patients must be trained to inform the patients about the lack of evidence of surgery, and that the trial is being conducted to ascertain the best choice in the future. This is important when recruiting patients, to reduce bias in favour of surgery.When designing this trial, we discussed several issues with the former leader of the Norwegian Patient Organisation for Spinal Pain. They are fully informed about the project. They will be involved in further interpretation and implementation of the study, preferably in collaboration with other patients who have undergone neck surgery.The designated investigator staff will enter the data required by the protocol into eCase report forms (eCRF). The investigator is responsible for assuring that data entered into the eCRF is complete and accurate, and that entries are made in a timely manner. The Clinical Data Management System (CDMS) used for eCRF in this study is ViedocTM. The setup of the study-specific eCRF in the CDMS will be performed by the Clinical Trial Unit, Research Support Services, Oslo University Hospital. After database locking, the investigator will receive a digital copy of the subject data for archiving at the investigation site.Data management will be performed by the Clinical Trial Unit, Research Support Services, Oslo University Hospital. The data-management procedures will be performed in accordance with the department’s Standard Operating Procedures (SOPs) and International Council for Harmonisation (ICH) guidelines. The data-management process will be described in the study-specific data handling plan and the study-specific data handling report after database closure.After database closure, the data will be stored in a dedicated and secured area at OUS. Data will be stored with all identifiers removed, where each study participant can only be recognised by his/her unique trial subject number.We have been granted approval by The Committee of Medical Ethics in Health Region South-Eastern Norway and from The Research Board at Oslo University Hospital, Norway. Standard informed written consent will be obtained from each participant. The trial is formally registered at the National Register, and Clinical Trials and will be reported according to the CONSORT  statement . The finPublished protocols include a Dutch trial comparing the effectiveness of surgical treatment and a wait-and-see approach including information about the nature and prognosis of the problem along with trustworthy counselling in patients with cervical radiculopathy caused by disc herniation . In addi


Gastric cancer is the fourth leading cause of deaths in Poland. The standard treatment for non-advanced gastric cancer is surgery, which significantly reduces the quality of life of patients. The objective of the study was to evaluate the strategy of coping with pain and its control, acceptance of illness, and adjustment to living with cancer in patients suffering from gastric cancer. The analysis of the impact of socio-economic factors on the above-mentioned problems was also analyzed. The study was conducted among 93 patients diagnosed with gastric cancer, treated on an outpatient basis at the Oncology Center—Maria Skłodowska—Curie Institute in Warsaw in 2017–2018. The PAPI (paper and pencil interview) technique was used. The questionnaire interview included metric questions (socio-economic variables) and four psychometric tests: BPCQ (the Beliefs about Pain Control Questionnaire), CSQ (the Pain Coping Strategies Questionnaire), AIS , and Mini-MAC  test. In the area of pain control, patients with gastric cancer assign the greatest role to internal factors , although women obtained the highest value in the impact of physicians. In the area of coping with pain, patients most likely select the strategy of praying/hoping . The mean value of acceptance of illness for patients with gastric cancer is M = 24.02, SD = 7.69, and it is not conditioned by any socio-economic variable. In the area of mental adjustment to illness, the highest values were obtained by positive reevaluation  and fighting spirit . Patients with gastric cancer control pain mainly through internal factors. The most frequently chosen strategy for coping with pain is praying/hoping, and positive reevaluation prevails in the field of mental adjustment. The results point to specific factors that can affect the patient’s pain, quality of life, and treatment outcomes. Knowing the diversity of these factors, it is possible to plan specific psychotherapeutic activities for specific groups of people that could be a supplement to the standard treatment process. Differences in the incidence of gastric cancer in the world significantly vary between populations. The highest incidence is observed in the eastern part of Asia , in Central America , in Eastern Europe , and in South America  .In the assessment of the health-related quality of life, the influence of psychological factors should also be emphasized. Literature indicates in particular such psychological factors as patients’ attitude towards disease, the ability to cope with stress and emotions, acceptance of the disease, or mental adjustment to the disease –10. The The objective of the study was to evaluate the strategy of coping with pain, pain control, acceptance of illness, and adjustment to life with cancer in patients suffering from gastric cancer. The analysis also included the impact of socio-economic factors  and chemotherapeutic treatment on the results obtained in psychometric tests.The Beliefs about Pain Control Questionnaire (BPCQ), designed to examine people suffering from pain . It consThe Pain Coping Strategies Questionnaire (CSQ), used to examine people who complain of pain . The queApproval Illness Scale (AIS), measuring the level of adjustment to illness . The AISMental Adjustment to Cancer (Mini-MAC), measuring the level of mental adjustment to cancer . The queThe study was conducted among 93 patients diagnosed with gastric cancer, who underwent radical resection and chemotherapy, being under outpatient care at the Oncology Center—Maria Skłodowska—Curie Institute in Warsaw in 2017–2018. The PAPI (paper and pencil interview) technique was used. The questionnaire interview included metric questions (socio-economic variables) and four psychometric tests:t test for independent samples, one-way analysis of variance, and Pearson’s r correlation. The assumed level of statistical significance is p < 0.05.The obtained results were subjected to statistical analysis using Student’s The study involved patients aged 23–84 , including 45 (48.4%) women aged 23–84  and 48 (51.6%) men aged 28–81 .Among the studied group of patients, 33 (35.5%) have primary/vocational education, 33 (35.5%) have secondary, and 27 (29.0%) have higher education. In towns with a population of up to 100,000 live 43 (46.2%) patients, and in cities with a population of over 100,000 live 50 (53.8%) patients. More than half of patients have a monthly net income of up to PLN 1500 , and 45 (48.4%) patients indicated that they achieved income over PLN 1500.00. There were 36 people (38.7%) working in the study group of patients, and 57 (61.3%) were pensioners.The Beliefs about Pain Control Questionnaire, measuring the strength of beliefs about pain control by means of 13 statements, characterizes patients as individuals controlling pain in person , the influence of physicians , or by random events.Patients with diagnosed gastric cancer control pain primarily due to internal factors , least frequently by random events , although the values of all dimensions are similar (Table p > 0.05). The age of patients positively correlated with locating pain control in random events (r = 0.246)—older patients attributed a greater role to this dimension.Pain control, mostly within internal factors, was the domain of men . Women obtained the highest value in the impact of doctors , but these differences proved to be statistically insignificant (p > 0.05). Similarly, there were no significant differences depending on the place of residence of the patients  (p > 0.05).Patients with primary/vocational education most often control pain through the impact of physicians , and patients with secondary and higher education attribute the greatest role to internal factors . A similar relationship was observed depending on the occupational status of patients; working people  attribute a greater role to internal factors than pensioners . In both cases, however, these differences are not statistically significant (p = 0.035). The mean value of the severity of location of pain control in random events was lower in the group of people with higher income  compared with the group with income below PLN 1500 per person in a household .Patients with higher income (over PLN 1500 per person in a household) achieved a much higher score in internal factors than patients with income below PLN 1500 per person in a household, but the statistically significant difference covers only the dimension of random events (p = 0.037).Internal pain control was assessed considerably higher by people who underwent chemotherapy in the last year  compared with people who did not receive chemotherapeutic treatment   and declaring coping . The lowest-rated strategies were reevaluation of pain sensations  and catastrophizing  (Table p > 0.05). A statistically significant negative correlation was found between the age of the patients and the reevaluation of pain sensations (r = − 0.245). Younger people more often chose a strategy for reevaluation of pain sensations than older people did.The strategy of pain control most often declared by women was praying/hoping, and in men, it was declaring coping. These differences are not statistically significant (p > 0.05). The chosen strategy of coping with pain does not depend on the place of residence (p > 0.05).Although praying/hoping was the most frequently chosen strategy by each group, divided into education , people with primary education obtained the highest score in this dimension . However, these differences are not statistically significant (p > 0.05).People with higher income (over PLN 1500 per person in a household) achieved slightly lower results for the praying/hoping or catastrophizing dimension than persons with income below PLN 1500 per person in a household. People with higher income, however, had higher scores for the dimensions of declaring coping or increased behavioral activity, however, these differences are not statistically significant (p = 0.003). Working people also obtained significantly higher scores in the dimensions of declaring coping and increased behavioral activity, but they were not statistically significant (p > 0.05).A statistically significant difference was obtained in the scope of reevaluation of pain sensations depending on the professional status of the patients. The mean value obtained in the group of pensioners  was statistically significantly lower than the mean value obtained in the working group  (p > 0.05).Chemotherapy treatment did not significantly affect the results obtained by the patients .The mean value of acceptance of illness in the group of women was M = 23.00 with a SD = 7.35 and was close to the mean value obtained in the group of men, which was M = 24.98 with a SD = 7.95. Acceptance of illness did not significantly correlate statistically with the age of patients (p > 0.05).The mean value of acceptance of illness in the group of people with primary or vocational education was M = 23.33 (SD = 8.26), in the group of people with secondary education was M = 24.55 (SD = 7.97), and in the group of people with higher education was M = 24.22 (SD = 6.79). Based on the value of the one-way analysis of variance, it was found that the differences were statistically insignificant .The mean value of acceptance of illness in the group of people living in towns with a population of up to 100,000 was M = 25.44 (SD = 7.70), and it was close to the mean value obtained in the group of people who lived in cities with a population of over 100,000 of M = 22.80 (SD = 7.54). Based on the Student’s t test value for independent samples, it was found that the difference received was irrelevant (p > 0.05).The mean value of acceptance of illness in the group of people with net income of up to PLN 1500 was M = 23.77 (SD = 7.60), and it was close to the mean value obtained in the group of people with income above PLN 1500, amounting to M = 24.29 (SD = 7.86). Based on the Student’s p > 0.05).The mean value of acceptance of illness in the working group was M = 25.22 (SD = 7.43), and it was close to the mean value obtained in the group of pensioners amounting to M = 23.27 (SD = 8.10), which was also a result that was not statistically significant (p > 0.05). The mean value of acceptance of illness in the group of people who underwent chemotherapy was M = 23.71 (SD = 7.18), and in the group of people who did not undergo chemotherapeutic treatment, it was M = 24.31 (SD = 8.20).Chemotherapy in the last year also did not affect acceptance of illness among the patients  in the Mini-MAC test, measuring mental adjustment to illness. A similar value characterized fighting spirit . The lowest result was obtained in the dimension helplessness-hopelessness  (Table p > 0.05).Among women, the dominant dimension of mental adjustment to illness was a positive reevaluation, and among men, fighting spirit. It was noticed that women obtained higher results in the dimensions of anxiety  and helplessness-hopelessness  in comparison with men , but they are not statistically significant. (p > 0.05). Similarly, education does not significantly affect the differences in patients’ adjustment to illness, although the mean higher values of anxiety in people with secondary education  and higher education  compared primary/vocational education  were observed.Age and place of residence do not determine the way of mental adjustment to illness (in both cases p > 0.05).Persons with lower income (below PLN 1500 per person in a household) achieved a higher result in terms of hopelessness and hopelessness  than people with higher income , but the differences were not statistically significant (p = 0.048).Comparing working people and pensioners, it was noted that the mean value of positive reevaluation was higher in the group of pensioners  than that among the working population  (p > 0.05).Chemotherapy did not affect the results obtained by the patients in terms of mental adjustment to illness  , 26.The study shows that patients with gastric cancer control pain mainly through internal factors . This was influenced by undergoing chemotherapy within the past 12 months. Patients who underwent chemotherapy obtained a higher score in the dimension of pain control through internal factors. As a comparison, in the case of another cancer of the digestive tract—colorectal cancer—patients also attributed the highest impact in controlling pain to internal factors  .The most common way of dealing with pain in patients with gastric cancer is praying/hoping  and declaring coping . In the case of colorectal cancer patients, the predominant strategies for coping with pain are declaring coping  and increased behavioral activity  . The lowIn the study by Kózka M. et al. conducted among 102 cancer patients hospitalized at oncology, radiotherapy and chemotherapy departments indicated that patients usually cope with pain through praying/hoping, and less often by declaring coping. The overall mean acceptance of illness for cancer patients on the AIS was M = 24.9 (SD = 6.35) . In our The study conducted by Kozak G. among patients with diagnosed gastric cancer, cancer of reproductive organs, pancreatic cancer, colorectal cancer, prostate cancer, staying in palliative care in the hospital or at home indicates that, in patients with gastric cancer, the degree of the intensity of fighting spirit grows with an increase of acceptance of the illness, whereas the level of anxiety and helplessness-hopelessness decreases. The average level of acceptance of illness at the AIS for patients with gastric cancer was significantly lower than in our study . As a comparison, in the study conducted by Kozak G., patients with pancreatic cancer reached the mean value of M = 18.23 (SD = 9.13), and with colorectal cancer M = 16.58 (SD = 7.42) . StudiesIn our study, patients with gastric cancer most often chose the strategy of positive reevaluation when it came to the mental adjustment to illness . However, studies conducted by Juczyński Z. indicate that anxiety and hopelessness-helplessness reach high values in patients with gastric cancer and pancreatic cancer . SimilarIn the case of patients with colorectal cancer, on the Mini-MAC scale, the constructive style dominates (M = 46.4 in comparison with M = 28.5 for the destructive style) with an advantage of fighting spirit (M = 23.9) and positive reevaluation (M = 22.5) . FightinSimilarly to the researches of other authors, the conducted study indicates that patients choose different types of adaptations to the disease or strategies for coping with pain. The adopted strategy significantly affects the quality of life of patients as well as the effectiveness of treatment –33. Due The awareness of the diversity of factors contributing to the selection of a particular strategy of adjustment to cancer makes it is possible to conduct specific psychotherapeutic activities for specific groups of patients that could supplement the standard treatment process. Constructive strategies for adapting to the disease should be an important element of education for both psychologists and doctors as well as for the patients themselves.There are limitations to every study design. In this study, tools measuring the time from the diagnosis of the disease to the date of testing were not used. It can be assumed that the longer the duration of the disease, the greater the acceptance of the disease. Nevertheless, the analysis of other studies published in this field suggests that our method is comparable with other research.Patients with gastric cancer control pain mainly through internal factors, although women have the highest mean in terms of the impact of physicians.Among the strategies for coping with pain, patients with gastric cancer most often indicated praying/hoping and declaring coping.The level of acceptance of illness among patients with gastric cancer reached the average result, and none of the variables examined significantly affected the level of acceptance of illness among patients.In terms of mental adjustment to illness, patients most often chose the style of positive reevaluation.The awareness of the level of disease acceptance or the strategy of coping with pain by specific groups of patients makes it possible to plan special psychotherapeutic activities for specific groups of patients.The significantly higher incidence of stomach cancer among men in Poland indicates that psychotherapeutic support in the fight against cancer should be addressed specifically to this group of people.


Epidural steroid injections (ESI) are commonly performed for the treatment of chronic cervical disc herniation (CDH). Although they are considered to be effective for both nociceptive and neuropathic types of pain, there is a lack of data regarding the impact of neuropathic pain (NP) and nociceptive pain components on treatment outcomes. The aim of this study is to compare the effectiveness of interlaminar epidural steroid injection (ILESI) between patients with predominantly NP and nociceptive pain due to CDH.Sixty five participants were initially included in the study and assessed by numeric rating scale (NRS), neck pain and disability scale (NPDS), short form-12 (SF-12), and self-reported Leeds assessment of neuropathic symptoms and signs (S-LANSS) pain scale at baseline and 1 month, 3 months, 6 months after ILESI.All patients were evaluated at 1st month and 3rd month follow-up periods while 54 of patients achieved to complete 6th month follow-up. There were significant improvements in all outcome measures for all time periods when compared with the pre-intervention scores. At baseline 24 (36.9%) of patients had predominantly NP in accordance with S-LANSS pain scale. The ratio of NP predominant patients reduced to 7.6% at 1st month, 12.3% at 3rd month, and 12.9% at 6th month with a significant difference for each follow-up period when compared with the baseline. Although all NRS and NPDS scores at baseline were significantly higher in patients with NP, improvement was significant at all follow-up periods in both groups. Minimal clinically important change in NRS was observed in >75% of patients at 1st, 3rd, and 6th month in both groups.The results of this study showed that NP is present in one-third of the patients suffering from neck and radiating arm pain due to CDH and cervical ILESI is an effective treatment approach for both neuropathic and nociceptive components of pain.Clinical Trials Registration Number: NCT04235478 NP tends to be more severe than nociceptive pain with distinctive characteristics thus it requires different treatment strategies.,4 In addition, it has been shown that NP is associated with a greater impairment in the physical, psychological, and social-related quality of life (QoL) with an increase in the treatment-related cost by 28% to 52% than the other forms of pain.,5 In order to determine the appropriate treatment strategy and get better outcomes, it is of utmost importance to identify both nociceptive and neuropathic components of pain in CDH.Cervical disc herniation (CDH) is frequently associated with neck and/or upper limb pain. It may consist of both nociceptive and neuropathic components. Pain in the upper limb may be caused by either nociceptive referred pain or neuropathic radicular pain. Nociceptive referred pain is caused by a noxious stimulation of structures such as muscles, joints, ligaments, and intervertebral discs of the spine, which induces upper limb pain in addition to the axial pain. Radicular pain is a frequent neuropathic pain syndrome in the upper limb and caused by mechanical compression or chemical inflammation of nerve roots and ectopic discharges originating from an irritated dorsal ganglion. These injections can be administered via interlaminar or transforaminal routes in the cervical spine. The transforaminal approach is associated with an increased risk for severe, life-threatening neurological complications. Therefore, interlaminar approach is often chosen to deliver the drug to cervical epidural space in daily practice. Although the exact mechanism of action of ESIs has not been fully elucidated yet, they are considered to have some favorable effects on the nociceptive and neuropathic pain generating signal transmission. Identifying characteristics of patients who are most likely to benefit from ESIs is important to prevent performing this invasive procedure to patients who have low probability of significant pain relief. Previous studies evaluating the effectiveness of cervical ESI for CDH have shown beneficial effects,,11 but there is limited data concerning nociceptive and neuropathic pain relief separately after cervical ESI. In an earlier study which aimed to define the clinical characteristics of patients who might have better outcomes after cervical ESI, it has been reported that patients with radicular symptoms and signs had more pain relief when compared with those with axial neck pain. In a recent study, Lee and Lee also analyzed both neck pain and radiating upper limb pain reduction after cervical ESI, however the comparison of the outcomes between patients with predominantly NP and those with nociceptive pain has not been previously studied.Epidural steroid injections (ESIs) are commonly performed procedures in the treatment of chronic CDH for long term pain relief.The aim of this study is to evaluate the effect of cervical interlaminar ESI (ILESI) on NP components of patients and to compare the outcome measures between patients with predominantly NP and nociceptive pain in order to determine the pain characteristic of patients who benefit more after cervical ILESI.22.1Patients between 18 and 75 years old having neck and radiating arm pain for at least 3 months, diagnosed with CDH by clinical examination and magnetic resonance imaging (MRI) findings were recruited in this prospectively designed study. All participants were unresponsive to physical therapy modalities and medical treatment including gabapentinoids, nonsteroidal anti-inflammatory drugs, and antidepressants. After recording a numeric rating scale (NRS) score of 4 or above, ILESIs were performed at Pain Medicine division of Marmara University School of Medicine between December 2017 and December 2019. Approval was taken from the ethics committee for the protocol (Ethics committee number: 2017/119) and it was registered in clinicaltrials.gov (Identifier: NCT04235478). Both written and verbal consents were obtained before the procedure. The exclusion criteria were having any other musculoskeletal disorder that may be related with patients’ neck and arm pain, systematic or local infection, bleeding diathesis, allergy to contrast substances or local anesthetic agents, presence of systematic inflammatory disease, malignancy or neurological illness, entrapment neuropathies of upper limb, myelopathy on MRI, history of cervical ESI in the last 3 months, and neck surgery. The participants were evaluated 4 times in total; before the intervention, 1 month, 3 months, and 6 months after the intervention. Neck/shoulder, arm, and night pain scores, disability, QOL, and neuropathic pain were assessed using NRS, neck pain and disability scale (NPDS), short form-12 (SF-12), and self-reported Leeds assessment of neuropathic symptoms and signs (S-LANSS) pain scale, respectively. Patients were divided into 2 groups with respect to their initial S-LANSS score. A score of below 12 was interpreted as a sign of having nociceptive pain, those with higher scores were accepted to have predominantly NP.2.22.2.1 There are 5 items regarding pain symptoms and 2 items involving self-administered sensory tests for the evaluation of allodynia and decreased sensation to pinprick. Responses to each item are yes or no and all items have specific weighted values. The score ranges from 0 to 24 and a score of ≥12 suggests the presence of NP. It has been demonstrated that Turkish version of S-LANSS is reliable and valid to identify the neuropathic pain.It is a 7-item self-reported scale developed to screen the presence of NP.NRS: It is a numeric scale with 11 point which ranges from 0 (no pain) to 10 (worst pain). It is a simple and widespread used scale for rating pain intensity. A minimal clinically important change (MCIC) scores for both neck pain and referred pain have been reported to be 1.5 for NRS.2.2.2 and validated in Turkish in 2004 by Biçer et al. The questions investigate the intensity of neck pain and its relationship with emotional factors and vocational, recreational, social, and functional aspects of living. A 10-cm visual analog scale (VAS) is used for each question. Scoring for each question ranges from 0 to 5 and the total NPDS score varies from 0 to 100 points. Higher scores indicate severe disability in patients.This scale is a functional assessment questionnaire specifically developed for patients with neck pain by Wheeler et alSF-12: This is one of the most widely used instruments to evaluate self-reported health related QOL. It is a shortened version of the SF-36 and covers the same 8 health domains, which reproduces 2 summary scores; mental component summary (MCS-12), and physical component summary (PCS-12). The scores range from 0 to 100 where higher scores indicated better QOL.2.33 of 2% prilocaine under sterilized conditions. After localizing C7–T1 interspace in anteroposterior view, the C-arm was adjusted to a contralateral oblique angle and under intermittent fluoroscopic imaging an 18G Touhy needle was advanced through right/left parasagittal part of C7–T1 interlaminar space. The loss of resistance technique was utilized to confirm that the needle was in the epidural space. A contrast medium was given to check non-vascularity and epidural spread prior to an injection of a mixture of 80 mg triamcinolone acetonide, 1 cm3 2% lidocaine hydrochloride, and 2 cm3 0.9% saline. The patients were discharged after 2 hours of observation period to be evaluated at 1st month follow-up.The procedure was carried by a pain physician having 10 years of experience in fluoroscopy guided interventions. Firstly, the patient was given a prone position and local anesthesia was applied with 3 cm2.4U was performed while the independent t test was used to compare normally distributed data. The Friedman test and Cochran Q test were conducted to determine changes over time with treatment for non-normally distributed data and repeated measures ANOVA was used for normally distributed data. Wilcoxon signed test, McNemar tests, and paired sample t-test were performed for pairwise comparisons with a Bonferroni correction for multiple comparisons. For Bonferroni correction, statistical significance was accepted at P-value <.0125 level, otherwise a P-value <.05 was considered statistically significant with 95% confidence intervals.Statistical analyses were performed using the SPSS version 20.0 software . Continuous variables were expressed in mean (standard deviation) and median (interquartile range), categorical variables were expressed in number and frequency. The chi-square and Fisher exact were used to compare categorical variables, where applicable. The Shapiro-Wilk test was used to analyze normal distribution of quantitative data. For the comparison of non-normally distributed data, the Mann–Whitney 3A total of 65 patients were recruited to the study. While patients were fully compliant with follow-ups until 3rd month, 11 patients did not admit to 6th month follow-up: 6 from nociceptive pain group, 5 from NP group. ILESI procedures were performed at C7–T1 level in all subjects, 4 of them had vasovagal reaction after the intervention, no major complications were observed. There were no significant differences in sociodemograpic and clinical characteristics of patients such as sex, age, body mass index and symptom duration between 2 groups  were significantly higher, referring to a better quality of life Tables . The numThe initial NRS scores for neck/shoulder pain, for arm and night pain were significantly higher in patients with NP. Post-intervention NRS scores for arm pain at 1st and 3rd month and for night pain at 3rd month were significantly higher in the NP predominant patients. All NRS scores were significantly reduced at all follow-up points when compared with baseline in both groups Table . MCIC fo4 This cascade plays a role in development and maintenance of central sensitization-related NP. The current study showed that 24 of 65 patients (36.9%) had NP symptoms and signs in accordance with the S-LANSS pain scale at baseline, indorsing the role of these pathophysiological mechanisms in this condition. In a previous study which evaluated the presence of NP in patients with unilateral cervical radiculopathy, 30% of patients demonstrated a NP component according to the PainDETECT questionnaire. In the current study all CDH patients with neck and radiating arm pain were included. The S-LANSS pain scale has a high sensitivity (83%) and specificity (87%) for the diagnosis of NP and has been widely used for investigating the effectiveness of different treatment modalities in NP.,21 Although there is no study in patients with CDH or cervical radiculopathy, it is an accepted questionnaire to depict pain with predominantly neuropathic origin and even offered as a diagnostic tool in lumbar radiculopathy.In the present study, the effects of ILESI on NP in patients with CDH were evaluated and the outcomes of patients with predominantly NP and nociceptive pain were compared. Herniated nucleus pulposus induces inflammation of the affected dorsal root ganglion and spinal nerves resulting in ectopic firing which is associated with increased glial activity in the spinal cord and the release of pain modulation agents.,10,23 In the literature, although there is no data about the effects of ILESI on NP components of CDH, there are studies showing the effectiveness of ESIs on NP in patients with low back pain.,25 The ESI exerts its anti-inflammatory effects on NP by reducing cytokine and chemokines, reducing or inhibiting neuroglial activation, inhibiting nociceptive C-fiber transmission and ectopic neuronal discharge and has stabilization effects by alleviating inflammation of the spinal nerves and epidural zone.,26 Compared with those with nociceptive pain, the initial NRS and NPDS scores were significantly higher in the NP predominant patients. The NRS-arm at 1st and 3rd month and the NRS-night scores at 3rd month were also found to be higher in the same group. The intensiveness of NRS scores and NPDS scores in NP group indicate that NP predominant patients experience severe pain and disability than those with nociceptive pain, consistent with previous studies. The relatively poor treatment outcomes among the NP predominant patients compared with those with nociceptive pain can be attributed to the structural alteration of the synapses in the cornu of the spinal cord, interneurons, and glial cells which are involved in the development and chronicity of NP, and glial activation-induced central sensitization. In other respects, the fact that the initial pain scores in patients with NP were higher than those with nociceptive pain may be the reason for the difference between the 2 groups during follow-ups. On the other hand, the ratio of patients with MCIC were similar between groups at any time points which suggests that ILESI is effective in both nociceptive and neuropathic components of pain and the NP symptoms and signs before the intervention do not adversely affect the treatment outcomes.The ratio of patients with predominantly NP decreased from 36.9% to 7.6% at 1st month, 12.3% at 3rd month, and 12.9% at 6th month after ILESI, indicating a statistically significant difference at all time points. In addition, significant improvements were also observed in the S-LANSS, NRS, SF-12, and NPDS scores at all post-intervention time points, which are compatible with previous studies showing reduced pain and disability and advanced QoL after ILESI in patients with CDH. In addition to S-LANSS scale, performing electroneuromyography for the diagnosis of an underlying radiculopathy which is the main cause of NP in patients with CDH could have increased the strength of the study. Nevertheless, the main strengths of the present study are its prospective design and novel findings on the effects of ILESI on NP in patients with CDH.Lack of a control group in consequence of ethical considerations and a relatively short follow-up period are the main limitations of this study. Radiologic assessment of the groups regarding nerve root compression grading, which might affect outcomes after ILESI was also omitted. Furthermore, S-LANSS scale might have missed some of the NP predominant cases. Although it is a useful tool to establish the presence of NP, about 20% to 30% of the patients with NP can be overlooked.In conclusion, the results of this study showed that NP is predominant in about one-third of the patients suffering from neck and radiating arm pain due to CDH. These patients have higher neck, arm and night pain and disability scores when compared with those with nociceptive pain. Cervical ILESI is an effective and safe approach for the treatment of CDH, besides alleviating both nociceptive and neuropathic components of pain, it also reduces disability. In addition, the response to the ILESI of patients with NP is comparable to those with nociceptive pain, despite the presence of initial higher pain and disability scores.Conceptualization: Canan Sanal-Toprak, Savas Sencan, Osman Hakan Gunduz.Data curation: Ekim Can Ozturk, Feyza Nur Yucel, Savas Sencan.Formal analysis: Ekim Can Ozturk, Feyza Nur Yucel, Savas Sencan.Investigation: Canan Sanal-Toprak, Ekim Can Ozturk, Feyza Nur Yucel, Savas Sencan.Methodology: Ekim Can Ozturk, Feyza Nur Yücel, Savas Sencan.Supervision: Canan Sanal-Toprak, Savas Sencan, Osman Hakan Gunduz.Writing – original draft: Ekim Can Ozturk, Feyza Nur Yucel, Savas Sencan.Writing – review & editing: Canan Sanal-Toprak, Savas Sencan, Osman Hakan Gunduz.


To assess the pain intensity of two intracameral anesthetic solutions in patients undergoing cataract surgery and evaluate the factors influencing the patients’ postoperative activities.Sixty-two patients undergoing cataract surgery were randomized to receive the study drug – a manufactured solution of 0.02% tropicamide/0.31% phenylephrine/1% lidocaine (Mydrane) or a traditional anesthetic formulation - solution of 1% lidocaine/0.025% adrenaline as an intraocular anesthetic. The pain intensity was assessed by Visual Analog Scale for Pain (VAS Pain) and Brief Pain Inventory-short form (BPI) on the next day after the surgery.p = 0.51). There were no statistically significant differences between the two anesthetic methods with respect to pain intensity during the surgery (p = 0.94) and the influence of pain during the last 24 h on activity (p = 0.79), mood (p = 0.31), social contacts (p = 0.29), sleep (p = 0.5) and the joy of life (p = 0.39). Additionally, there was no statistically significant influence of age, sex, lateralization, co-existing ophthalmological diseases (p = 0.98) and post-operative complications (p = 0.4) on the experienced pain measured during the surgery and in the last 24 h.The mean pain score measured preoperatively with VAS Pain was 0.34 in Mydrane group and 0.09 in the reference group  seems to be as effective as off-label traditional anesthetic formulation, in reducing the pain experienced during cataract surgery under topical anesthesia. Since the 1990s, cataract surgery has progressed to the modern technique of phacoemulsification that involves a small corneal incision and the implantation of a foldable intraocular lens (IOL). This surgical procedure no longer requires complete akinesia, thus, encouraging the use of less invasive anesthetic modalities .In the last decade, peribulbar, retrobulbar, and sub-Tenon’s anesthesia were the most popular techniques used during cataract surgery . HoweverThe new NICE guideline (2017) for the management of cataracts in adults offers the possibility of use intracameral anesthesia for cataract surgery.The study drug - Mydrane™  is a fixed-dose mydriatic/anesthetic combination (0.02% tropicamide/0.31% phenylephrine/1% lidocaine) preservative-free, approved for intracameral use during cataract surgery. The study drug is a very appealing formulation because it represents a safe and effective combination of anesthetic and mydriatics . FurtherVisual Analog Scale (VAS) for Pain and Brief Pain Inventory (BPI) are new tools developed to assess the pain in quantitative terms. The VAS has been validated  and usedThe BPI allows patients to rate the severity of the pain and grade how their pain interferes with common feelings and functions. Although BPI was initially developed to assess pain related to cancer , it has To date, some studies have compared different types of cataract surgery anesthesia . HoweverThe aim of the present study was to compare patient-reported pain intensity of two types of intracameral anesthetic solutions  for phacoemulsification and identify the factors affecting pain intensity using VAS and BPI in both groups. The null-hypotheses being tested is that eyes randomized to the study drug will have postoperative pain intensity the same or less than those randomized to traditional intracameral Lidocaine formulation.The study was conducted at the Department of General Ophthalmology of Medical University in Lublin, Poland. The study protocol conformed to the principles of the Declaration of Helsinki and was approved by the Local Research Ethics Committee (n° KE-0254/342/2018) and was registered on ClinicalTrials.gov (ID: NCT04166578).A written informed consent form, for the processing of personal data, was obtained from all patients.It was a prospective, one-center, single-blind, pilot, randomized study. Patients were randomly selected to the group receiving intracameral the study drug - manufactured solution of 0.02% tropicamide/0.31% phenylephrine/1% lidocaine (Mydrane™) (0.2 ml) or traditional intracameral formulation based on 1% lidocaine and 0.025% adrenaline (0.2 ml) during phacoemulsification.Inclusion criteria were as follows: age above 18 years, best corrected visual acuity (BCVA) of 0.2 logMAR or worse, and agreement for taking part in the study.Exclusion criteria were as follows: psychiatric diseases, epilepsy, ongoing treatment with hypnotics or psychotropic drugs (including opioids) within a week before admission, daily analgesic treatment, intake of additional rescue medications due to the pain after surgery, omitting postoperative visits. The patients who later needed additional medications for pain relief were excluded as it would be difficult to assess which medication is responsible for the achieved scores in psychometric measurements.After inclusion in the study, the enrolled patients were randomly assigned, in a 1:1 ratio, to one of two groups related to the type of anesthesia, in a single-blind manner using computer-generated codes.Diabetes mellitus was noted in 28.57% (n = 18) (9 in the study group and 9 in the reference group).All patients received 1 drop of levofloxacin  at 60 min, 30 min, and 15 min before surgery. Topical anesthesia with 1 drop of 0.5% proparacaine  was given to all the patients at 30 min, 15 min, and 5 min before surgery. No general sedation was administered before surgery.After asepsis of the periocular skin with chlorhexidine 0.5% and a drop of povidone-iodine 5.0%, the eyelid speculum was carried out. The Constellation System  was used with the standardized use of a microtip 30-gauge cannula. All surgeries  were performed by two experienced surgeons (RR and KN). The main incision was created on 3 planes of approximately 1.8 mm of extension with a triangular blade of 2.75 mm at the 10 o’clock position. In the Mydrane group, 0.2 ml of Mydrane™ was injected into the anterior chamber. In the reference group, a combination of lignocaine 1% lidocaine and 0.025% adrenaline (0.2 ml) was injected into the anterior chamber. Next, the anterior chamber was filled with methylcellulose 2.0%, and paracentesis in the surgical limbus was performed at the 2 o’clock position. A continuous curvilinear capsulorhexis approximately 5.5 mm in diameter, a hydrodelineation, and hydrodissection with balanced salt solution  were performed. A stop-and-chop technique was performed. The cortex was aspirated with an irrigation/aspiration pen, and the IOL was implanted in the capsular bag using an injector and a cartridge. The incision was sealed by incisional edema with BSS. During the first 7 days after surgery, levofloxacin (Oftaquix) eye drops were applied every 4 h in combination with 0.1% dexamethasone (Dexafree) in a tapering schedule over the subsequent 20 days.The pain was assessed quantitatively 15 min before and after the end of surgery with VAS by an ophthalmologist other than the surgeon, and masked to the used anesthetic method. A unidimensional VAS 10 cm in length  was used, with its numbers (degrees) being visible only on the side of the examiner . Before A third measurement was taken the next day after surgery using the BPI-short form, which is a widely used measurement tools for assessing clinical pain. It contains two domains that measure pain intensity (severity) and the impact of pain on functioning (interference). In the current study, BPI was used to evaluate the severity of pain and the impact of pain on daily function in the previous 24 h. The responses were given using an eleven-point numeric rating scale (NRS) scored 0–10, where 0 = best outcome/does not interfere/no pain/complete pain relief and 10 = worst outcome/completely interferes/most pain/no pain relief.A full ophthalmological examination had been carried out before and 7 days after the surgery. BCVA, slit-lamp biomicroscopy and fundus examination were evaluated. The intraocular pressure was also measured. Coexisting eye diseases and post-operative complications were noted.The patients were not offered any oral or topical anesthetics until they filled out the BPI. None of the patients reported a need to use any analgetics after surgery.The obtained results were subjected to statistical analysis. The values of the measurable parameters analyzed were presented using the mean value, median, quartiles, and standard deviation, and for the unmeasurable ones using the number and percentage. For measurable features, the normality of the distribution of the analyzed parameters was evaluated using the W Shapiro-Wilk test.To compare the two groups, the Mann-Whitney test was used. The Spearman R test was used to assess the relationship between variables. For dependent variables, the Wilcoxon Pair Order test or the Character test was used. For unrelated qualitative features, the Chi2 homogeneity test was used to detect the existence of differences between the compared groups. The Chi2 test of independence was used to investigate the existence of dependencies between the examined features.p value ≤ 0.05 was considered statistically significant. All calculations were performed using STATISTICA 10 PL StatSoft.A Initially, a total of 70 patients were scheduled to participate in the study. However, 8 patients did not attend postoperative visits and were excluded. As a result, only 62 patients were included in the analysis . In the study group, the patients’ age was 75.20 ± 8.46, while in the control group - 72.45 ± 5.89. The ratio of women to men was 55.13% vs. 45.88% in the study drug group and 53.61% vs. 47.39% in the traditional formulation group. The average duration of surgery in the whole group was 11.53 ± 3.30 min. In the study group, the operation time was 11.61 min, while in the control group 11.44 min. The obtained results are presented in p = 0.51). Moreover, the mean pain (± SD) measured with VAS Pain at the end of the surgery also revealed no statistically significant differences between the study drug and traditional formulation groups .At baseline before the surgery, 7 patients (11%)—5 in the study drug group and 2 in the traditional formulation group—reported ocular pain. The mean pain measured with VAS Pain was 0.34 in the study drug group and 0.09 in the traditional formulation group. There were no statistically significant differences between the two groups (The range of pain measured on the next day after surgery with BPI-short form was as followed:p = 0.94).There were no differences in the mean severity score between the study drug and the traditional formulation groups (p = 0.79), mood (p = 0.31), social contacts (p = 0.29), sleep (p = 0.5) and the joy of life (p = 0.39). We found only statistically significant differences in the ability to walk (p = 0.03) and everyday duties (p = 0.01).There were no statistically significant differences between the two groups with respect to the influence of pain during the last 24 h on activity (p = 0.03)  was significantly higher in the study drug group as compared to the traditional formulation group .In addition to cataract, other ophthalmological conditions/diseases were observed in 13 (42%) patients in the study drug group and 17 (54%) patients in the traditional formulation group. These conditions were glaucoma , diabetic retinopathy , retinitis pigmentosa , age-related macular degeneration , idiopathic epiretinal membrane , pseudoexfoliation syndrome , and high myopia . Moreover, there were no statistically significant differences between the two groups (Sixteen (52%) patients in the study drug group and 14 (45%) in the traditional formulation group underwent operation of the right eye. For 7 patients in the study drug and 5 patients in the traditional formulation group, the cataract surgery was performed on the first eye.p = 0.4) regarding postoperative complications. Eleven cases in the study drug group had corneal edema. In the traditional formulation group, 5 patients had corneal edema, 2 postoperative rise of intraocular pressure, 1 iris damage, and 1 hemorrhage into the anterior chamber.We did not find statistically significant differences between the two groups . The factors affecting pain during surgery and the time of the surgery influencing on pain in the traditional formulation and the study drug group are listed in There was no statistically significant influence of age, sex, lateralization, co-existing ophthalmological diseases, time of surgery, and post-operative complications on the experience of pain measured with VAS Pain during the surgery and on pain severity mean score and pain interference measured with BPI-short form (p = 0.03) but similar mean severity pain score. Moreover, the mean severity pain score and pain interference did not differ in the study drug group when the order of the surgery was considered.In the traditional formulation group, the patients who underwent second versus first cataract surgery showed a significant higher pain interference (p = 0.0008 vs. p = 0.0006).BCVA was similar after the operation in both groups (p=0.66). Mean BCVA (± SD) after surgery was lower in the study drug group vs. the traditional formulation group . When preoperative and postoperative BCVA values were compared, visual acuity improved significantly in both groups (p = 0.003) in the study drug group. A correlation between BCVA and postoperative complications in the traditional formulation group (p = 0.004) was noted. Postoperative BCVA did not correlate with pain intensity measured with VAS and BPI  in both groups.There was a significant dependence between postoperative BCVA and co-existing diseases of the eye . To estimate the pain intensity, we used two psychometrical tools: VAS Pain and BPI. The mean pain intensity measured with VAS Pain at the end of surgery was on the level 1.15 (SD ±1.8) in the study drug group and 1.90 (SD ± 2.7) in the traditional formulation group. These results are comparable with that of Tan et al.’s study . Also, KPrevious studies have also evaluated factors affecting pain intensity during cataract surgery . In our We suspected that age might have affected the pain during surgery. It has been shown that aging may impact pain perception and expression . UnpleasOur results also showed no correlation between gender and pain, as previously shown by Also, lateralization did not influence pain during phacoemulsification. This finding is similar to the results shown by In our study, we did not find any correlation between other ophthalmological conditions, postoperative complications, and pain. Some authors tried to determine factors affecting patients’ pain intensity during “in office” intravitreal injection procedure but did not observe correlation between ophthalmological diagnosis and pain intensity . SimilarIn our study, visual acuity improved after cataract surgery, but it did not affect pain severity and pain interference. In a previous study about intravitreal injection, visual acuity improvement did not decrease pain intensity before the procedure .According to the mechanism of pain development during cataract surgery, there are two possibilities. Firstly, the surgical manipulation triggers the arachidonic acid cascade, which is responsible for the production of inflammatory mediators such as prostaglandins . ClinicaSecond, the stimulation of ciliary nerves during manipulation of the iris and stretching of the ciliary and zonular tissues can produce discomfort. An injection of 1% lidocaine through the side port incision provides sensory blockage of the iris and ciliary body  and, thereby, relieves discomfort experienced during IOL placement .According to our results, the study drug Mydrane™ and the traditional anesthetic formulation seems to have similar efficacy in attenuating pain. Other studies indicated Mydrane™ to be effective also as an intraoperative mydriatic . For theIn summary, our study shows that the study drug Mydrane™, seems to be as effective as off-label anesthetic formulation, in reducing the pain experienced during cataract surgery under topical anesthesia, improving patients’ cooperation and satisfaction. Although several combinations of intracameral agents are being used during cataract replacement procedures, the only EMA-approved product for this use is Mydrane™ formulation. Further randomized clinical trials with a larger sample size are required to better investigate the effect of Mydrane™ formulation during complicated cataract surgery and other surgical ocular procedures.All datasets generated for this study are included in the article/The studies involving human participants were reviewed and approved by Local Research Ethics Committee, Department of General Ophthalmology, Medical University of Lublin, Poland (KE-0254/342/2018). The patients/participants provided their written informed consent to participate in this study.MT and RR: conceptualization, design of the study and project administration as Principals Investigators. MT and DN wrote the first draft of the manuscript. MR, TA, KN, CB and CC: revision and validation of the manuscript. AB and PM: data curation and statistical analysis. All authors gave final approval of 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.


To evaluate ultrasound-guided inactivation of myofascial trigger points (MTrPs) combined with abdominal muscle fascia stripping by liquid knife in the treatment of postherpetic neuralgia (PHN) complicated with abdominal myofascial pain syndrome (AMPS). n = 33) including those with PHN and without myofascial pain syndrome (MPS) and control group 2  including those with PHN complicated with MPS and observation group 1  including those with PHN complicated with limb myofascial pain syndrome (LMPS) and observation group 2  including those with PHN complicated with AMPS. All groups received zero-grade treatment: routine oral drugs and weekly paraspinal nerve block. PL and PA groups were also treated step by step once a week: primary ultrasound-guided inactivation of MTrPs with dry needling, secondary ultrasound-guided inactivation of MTrPs with dry and wet needling, and tertiary ultrasound-guided dry and wet needling combined with muscle fascia stripping by liquid knife. At one week after primary treatment, patients with a VAS score > 2 proceeded to secondary treatment. If the VAS score was <2, the treatment was maintained, and so on, until the end of the four treatment cycles. Pain assessment was performed by specialized nurses at one week after each treatment, including VAS score, McGill pain questionnaire (MPQ) score, pressure pain sensory threshold (PPST), and pressure pain tolerance threshold (PPTT). VAS score was used as the main index and VAS <2 indicated effective treatment. At 3 months after treatment, outpatient and/or telephone follow-up was performed. The recurrence rate was observed and VAS > 2 was regarded as recurrence.  From January 2015 to July 2018, non-head-and-neck PHN patients in the Pain Department, The First Affiliated Hospital of Soochow University, were treated with routine oral drugs and weekly paraspinal nerve block for two weeks. Patients with 2 < VAS  score < 6 were subjects of the study. They were assigned into control group 1 . At one week after secondary treatment, the effective rate was 100% and 37.5% in PL and PA groups, respectively, with significant difference between the groups (P < 0.05). The effective rate increased to 90.6% in PA group at one week after tertiary treatment. At one week after the end of treatment cycles, the scores of VAS and MPQ were significantly lower in C1, PL, and PA groups than in C2 group (P < 0.05), while PPST and PPTT were significantly higher than in C2 group (P < 0.05). There was no significant difference between C1 group and PL group (P > 0.05). At follow-up at 3 months after treatment, the recurrence rate was low in each group, with no significant difference between the groups (P > 0.05).  At one week after primary treatment, the effective rate was 66.7% in PL group, significantly higher than that in PA group (15.2%,  About 57% of PHN patients with mild to moderate pain are complicated with MPS, and ultrasound-guided inactivation of MTrPs with dry and wet needling can effectively treat PHN patients complicated with LMPS. However, patients with PHN complicated with AMPS need to be treated with ultrasound-guided MTrPs inactivation combined with muscle fascia stripping by liquid knife as soon as possible. Patients with postherpetic neuralgia (PHN) suffer from persistent and severe breakthrough pain, which may arise from nerve changes due to virus infection or immune response , 2. Somen = 33) including patients with PHN and without MPS, control group 2  including those with PHN and MPS and observation group 1  including those with PHN and LMPS  and observation group 2  including those with PHN and AMPS . Male or female patients aged 40∼85 years who were clearheaded, had no communication disorder, and were able to take oral medicine were included. Written informed consent for pain treatment was obtained before treatment, and this study was approved by the Ethics Committee of our hospital.From January 2015 to July 2018, patients with non-head-and-neck PHN were treated in the Pain Department, The First Affiliated Hospital of Soochow University. Routine treatment was given on the day of initial diagnosis, paravertebral nerve block at corresponding spinal cord segments at the lesion site (once a week), and oral drugs  or gabapentin , amitriptyline ). After two weeks of routine treatment, those with 2 < VAS < 6 were included in the trial. A total of 256 PHN patients met the preliminary screening criteria, including 110 patients without MPS, 48 PHN patients with MPS, 65 PHN patients with LMPS, and 33 AMPS patients with MPS. Therefore, 33 patients were randomly selected from 110 patients with PHN without MPS, 33 from 48 patients with PHN and MPS, and 33 from 65 patients with PHN and LMPS. A total of 132 patients were enrolled in the experiment. The patients were assigned into 4 groups, control group 1 , gabapentin capsule  and amitriptyline tablets .Ropivacaine hydrochloride , Diprospan , and 0.9% sodium chloride injection.(1) Formula for Paravertebral Nerve Block and Wet Needle (Formula 1). Diprospan 1/2 (containing betamethasone dipropionate 2.5 mg and betazone sodium phosphate 1 mg), 0.75% ropivacaine hydrochloride 4 ml, diluted to 20 ml with 0.9% sodium chloride injection. At a dose of 8 ml for each paraspinal block, paravertebral block of a maximum of two segments was performed t at one time. The method of paravertebral nerve block is omitted.(2) Formula for Liquid Knife (Formula 2). 0.75% ropivacaine hydrochloride 4 mL diluted to 20 ml with 0.9% sodium chloride injection.The needle used in the study was dental no. 5 long needle , and the ultrasonic diagnostic instrument was manufactured by Sonosite Company of the United States, with a probe frequency of 6 × 13 MHz.For intervention to increase the accuracy of inactivation of MTrPs with dry and wet needle, ultrasound imaging was used to avoid unintentional damage to these important structures, with no irradiation delivered to the patients. The body was examined in advance and marked on the skin with definite tenderness points. The mark points were located in the center of the ultrasonic probe and guided in real time by in-plane technology. The skin was sterilized by Hexial 2% solution (ethanol + chlorhexidine gluconate 2%), and a sterile surgical towel was placed on the patient. A linear array transducer probe was used to scan the marked area in the sagittal and axial planes. Initially, the dental long needle was used to identify the muscle and its fascia. MTrPs showed oval, locally heterogeneous hypoechoic or significant hyperechoic region under two-dimensional ultrasound. The MTrPs were punctured repeatedly with dental needle No. 5 under the guidance of ultrasound to induce obvious aching and distending pain, with no focus on the induction of local twitch responses (LTRs), especially in patients with AMPS, but if LTRs could be induced, the points were punctured as many times as possible until LTRs could not be induced.The standard of MTrPs inactivation with dry needling, aching, and distending pain induced by needling of MTrPs disappeared or were significantly alleviated, and LTRs disappeared.Wet needle, after inactivating MTrPs with dry needling, Formula 1 was drawn with 2 ml syringe and injected into and around MTrPs, 1 ml per MTrP, and up to 5 MTrPs were injected at a time see .The preparatory steps used in the treatment of muscular fasciae stripping by liquid knife were identical to those described above of the dry and wet needle inactivation trigger point. The body was examined in advance and marked on the skin with definite tenderness points. The mark points were located in the center of the ultrasonic probe and guided in real time by in-plane technology. The needle tip passed through the muscle fascia with obvious tenderness, and the muscle fascia space which showed significant aching and distending pain or convulsions induced by needling was taken as the target site. First, the muscle fascia was punctured repeatedly until pain disappeared or was significantly alleviated and local convulsions resolved, and then Formula 2 was injected. The muscle fascia was stripped with the liquid. 3∼5 ml was injected into each site, and the muscle fascia was stripped as much as possible, with injection of up to three sites at a time see .All treatments and interfascial injection were administered by the same physician, but assessments and follow-up were conducted by other investigators who were not aware of group assignments.All groups received zero-grade treatment, routine oral drugs and weekly paraspinal nerve block. PL and PA groups also received weekly step-by-step treatment. The first level was ultrasound-guided inactivation of MTrPs. Secondary treatment was ultrasound-guided inactivation of MTrPs with dry and wet needling. Tertiary treatment included ultrasound-guided dry and wet needling combined with muscle fascia stripping by liquid knife. One week after the first-level treatment, the patient's VAS score was >2 points, and the second-level treatment was entered. If the VAS score was <2 points, the current level of treatment was maintained, and so on. The treatment period was four weeks.(1) Evaluation Tool. Pain assessment was performed by specialized nurses at one week after each treatment, including VAS score, MPQ score, PPST and PPTT. The VAS score was critical, with VAS <2 indicating effective treatment and VAS >2 indicating ineffective treatment, and the effective rate was calculated as the number of patients responding to treatment/total number of patients treated. At 3 months after the end of treatment cycles, outpatient and/or telephone follow-up was performed to observe the recurrence rate. VAS >2 was regarded as recurrence in patients responding to treatment previously, and the recurrence rate was calculated as the number of patients experiencing recurrence/the number of patients responding to treatment at one week after the end of treatment cycles.(2) VAS. The VAS was a 10 cm horizontal line labeled no pain at one end and worst imaginable pain at the other end. The patients were asked to mark on this line where the intensity of the pain existed. The distance from no pain to the patients' mark numerically quantified the pain. The VAS was a simple and efficient method that correlated well with other reliable methods.(3) McGill Pain Questionnaire (MPQ). The MPQ had three parts; the first assessed pain quality and yielded a sensory score , an affective score , and a total score (sum of the sensory and effective scores). The second part of the short form (SF)-MPQ consisted of a 100 mm VAS of pain intensity that patients used to rate their pain during the preceding week. The third part of the SF-MPQ was a measure of present pain intensity (PPI) using a 6-point scale .(4) Tenderness Threshold Measurement. After palpation, the test end of the pressure pain tester  was used to gradually contact the skin and was required to be perpendicular to the skin. PPST and PPTT were measured. The peak mode was adopted in the test, and the unit of the scale was kg/cm2 with a measurement range of 1∼10 kg/cm2. PPST was the level of pressure that subjects felt with the change from pressure to pain. PPTT was the maximum pressure that subjects could tolerate. Usually a maximum value was set, and when pressure reached the value, test was stopped even if the subject still tolerated the pressure, and the maximum value was regarded as PPTT. Measurement was performed for a total of 5 times at an interval of 10∼15 s, and the mean was taken as pain threshold.(5) Adverse Reactions. The adverse reactions related to treatment were truthfully recorded, including nausea, vomiting, lethargy, subcutaneous bleeding, allergic reactions, panic, and dizziness.n (%). The independent-samples t-test was used for statistical analysis of the continuous data, and the Chi-squared test was used for statistical analysis of the categorical data. The repeated-measures analysis of variance (ANOVA) test was used to compare data between the two groups before and after treatment. P value <0.05 was considered to represent a statistically significant difference.All data were analyzed using SPSS 23.0 . At different time points, there are individual patients falling out, and the data of the patients falling out are not counted. The data were presented as the mean ± SD or P > 0.05). Results were presented in There were no significant differences in age, gender, weight, duration of PHN, cardiac disease, pulmonary disease, liver and renal diseases, metabolism, and nutrition disorders between the four groups (P < 0.05). At one week after secondary treatment, the effective rate was 100% and 37.5% in PL and PA groups, respectively, with significant difference between the groups (P < 0.05), and the effective rate in PA group increased to 90.6% at one week after tertiary treatment. See At one week after primary treatment, the effective rate was 66.7% in PL group, significantly higher than that in PA group , while PPST and PPTT were significantly higher than those before treatment (P < 0.05). The scores of VAS and MPQ were significantly lower in C1, PL, and PA groups than in C2 group (P < 0.05), while PPST and PPTT were significantly higher than those in C2 group (P < 0.05), but there was no significant difference between C1 and PL groups (P > 0.05). The scores of VAS and MPQ were slightly higher in PA group than those in C1 and PL groups, while PPST and PPTT were slightly lower than those in C1 and PL groups, with no significant difference (P > 0.05). See At one week after the end of treatment cycles, the scores of VAS and MPQ in the four groups were significantly lower than those before treatment (P < 0.05). Among the former three groups, the effective rate was slightly higher in PL group than in the other two groups, but there was no significant difference (P > 0.05). At follow-up at 3 months after the end of treatment cycles, a very small number of patients in each group had recurrence, with the lowest recurrence rate in C1 group (3.8%). The recurrence rate was similar in the other three groups, but there was no significant difference among the four groups (P > 0.05). See At follow-ups at one week and three months after the end of treatment cycles, the effective rate was significantly higher in C1, PL, and PA groups than in C2 group (P > 0.05), as shown in Finally, in this study, adverse reactions were also observed, including nausea, vomiting, dizziness, somnolence, palpitations, chest tightness, bleeding, infection, and allergy in the four groups after treatment. The results showed that the adverse effects experienced in the four groups were not statistically different after treatment , tenderness threshold detected by pain detector, ultrasound imaging, electromyography (EMG), magnetic resonance elastography (MRE), thermal texture maps (TTM), etc. , 24. UltAt the same time, it is interesting to note that when the needle tip stimulated the MTrPs on the muscle fascia, the tangled muscle fascia stretched out instantly on the ultrasound image in some patients see . TreatmeFurthermore, we explored the effective treatment measures for PHN patients complicated with LMPS or AMPS, respectively. The results showed that the therapeutic effect of dry and wet needling was not as good in PA group as in PL group. The therapeutic effect was satisfactory only after combination with muscle fascia stripping by liquid knife. The difference in therapeutic effect may be due to the fact that in patients complicated with LMPS, stimulation of MTrPs in the muscle can mostly induce LTRs because of well-developed muscles of the limbs, which is enough to unfold the deformed and wrinkled muscle fibers, in turn, which interrupts the vicious circle of pain (PHN)-MPS pain. However, the abdominal muscle is relatively weak and usually covered by muscle fascia. Stimulation of MTrPs in the muscle fascia can generally not induce LTRs, and deformed and wrinkled muscle fascia can only stretch out with the help of physical stripping effect of the liquid knife.In addition, it is confirmed that local anesthetic injection in MTrPs can regulate the central sensitization of chronic pain , but it Limitations of this study are as follows. (1) The duration of follow-up in this study is not long enough, and only the recurrence rate at 3 months after the last treatment was followed up. In view of the intractable and refractory characteristics of PHN, observation and follow-up for a longer time will be performed in our further study. (2) The time point for assessment of treatment effect is one week after each treatment, which makes it difficult to tell whether the assessment results are cumulative effect of the previous treatment or effect of the new treatment method. (3) Substudy is not performed on duration of PHN because of the small sample size. Although the mean duration of PHN in each group is not statistically significant, clinical experience and literature research have told us  that theIn summary, the trigger point related theory holds that tenderness amplification and involved pain caused by MPS are the important causes of chronic pain, and it is confirmed that MPS is a major complication of neuralgia. Therefore, patients with PHN complicated with MPS should be considered carefully in clinic. It will be better to start with the treatment of MTrPs in the presence of MPS. In this study, about 57% of PHN patients with mild to moderate pain are complicated with MPS, and ultrasound-guided inactivation of MTrPs with dry and wet needling can effectively treat patients with PHN complicated with LMPS. However, patients with PHN complicated with AMPS need to be treated with ultrasound-guided inactivation of MTrPs with dry and wet needling combined with muscle fascia stripping by liquid knife as soon as possible.