Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Rare Diseases

Breast Neoplasms

Pain

Chronic Pain

Breast Diseases

Skin Diseases

Neurologic Manifestations

Chronic Graft Versus Host Disease

Breast cancer survivors assigned to the experimental intervention will participate in 1 online PNE session followed by 3 PNE + MI sessions spread over 4 weeks. Each session will last for approximately 45 minutes and all sessions will be held in one-on-one format, allowing to individually tailor content to the patient's maladaptive beliefs and perceived injustice. After the first live session, breast cancer survivors will receive a perceived injustice-targeted PNE information leaflet that they need to read carefully at home.

Breast cancer survivors assigned to the experimental intervention will participate in 1 online biomedically-focused education session followed by 3 biomedically-focused education sessions spread over 4 weeks. Each session will last for approximately 45 minutes and all sessions will be held in one-on-one format in order to balance nonspecific treatment effects between treatment arms, the duration, format and number of sessions as well as the didactical approach will be identical in both treatment groups. After the first live session, breast cancer survivors will receive an information leaflet from 'Kom op tegen Kanker' regarding 'Pain in and after treatment' that they need to read carefully at home.

PNE is a cognitive behavioural intervention, including educating patients that pain is an output product of the brain resulting from input from multiple central and peripheral nervous system processes and leading to threat perception. Transferring that knowledge to patients, allows them to understand, accept and effectively cope with their pain. In order to obtain the targeted behavioural change, motivational interviewing is used as the communication process throughout PNE.

Pain Neuroscience Education (PNE)

Motivational interviewing is a directive, collaborative, patient-centered communication approach for eliciting and enhancing motivation for behaviour change by helping clients to resolve ambivalence and uncertainty.

Motivational Interviewing (MI)

The traditional biomedical-focused education programme explains patient's pain experience from a tissue (injured versus healthy tissue) and biomechanical perspective.

Biomedically-focused education

Laurence Leysen, Prof. Dr.

Eva Roose, Dra.

Brenda De Petter, Dr.

Jo Nijs, Prof. Dr.

Annick Timmermans, Prof. Dr.

Carine De Rop, Dr.

Breast cancer is the most frequently diagnosed cancer in women worldwide. An important portion of the breast cancer survivors will face chronic pain complaints. These pain complaints do not only impact the patient's quality of life but also prevents resumption of activities, leading to huge economic costs. 30% of all breast cancer survivors with pain present with perceived injustice which has been conceptualized as a multidimensional appraisal process characterized by a tendency to interpret one's losses as severe and irreparable, to attribute blame to others for one's suffering and to experience a sense of unfairness. Perceived injustice is also associated with increased opioid prescription and use, urging the need for targeted interventions to diminish perceived injustice.

Despite the fact that specific treatment plans for perceived injustice are not yet proven, pain neuroscience education (PNE) is proven to reassure and encourage towards activity. In order to obtain the targeted behavioural change, motivational interviewing (MI) is used as the communication process throughout PNE.

A multi-centre, parallel, two-arm, investigator-blinded study with 4-weeks intervention and two years follow-up will be conducted in 156 BCS with PI and pain. These will be randomly assigned to the intervention or usual care group. The groups will receive 1 online session, an information leaflet and 3 live sessions of education spread over 4 weeks. Pain neuroscience education in combination with motivational interviewing will be given in the experimental group and biomedically-focused education to the control group.

The primary scientific objective of the study is to examine whether perceived injustice-targeted PNE is superior to biomedically-focused pain education in reducing pain after 12 months in breast cancer survivors with perceived injustice and pain.

The secondary objectives of the study are to examine whether perceived injustice-targeted PNE, compared to biomedically-focused pain education, results in improving health-related quality of life, reducing perceived injustice and opioid use after 24 months in breast cancer survivors with perceived injustice and pain, and to conduct a health-care cost analysis which will finally result in a recommendation concerning the use of perceived injustice-targeted PNE in breast cancer survivors with perceived injustice and pain.

PI-targeted PNE+MI Compared to BIOMEDICAL Education in BCS

The Effect of Perceived Injustice Targeted Pain Neuroscience Education and Motivational Interviewing Compared to Biomedical Focused Education in Breast Cancer Survivors

After the project, the data will be archived in the VUB University Archive with restricted access. Data sharing is only permitted if all involved parties agree, and a Data Sharing Agreement has been signed.

Open Access will not be possible due to the high degree of confidentiality of the pseudonymized medical data, although all requests regarding sharing the research data will be considered by the parties.

The university server is equipped with user-level access permission management. Participants' personal data will be coded, and system encryption will be used to protect the coded data.

No costs are expected, but project and/or research group funds will cover any potential data sharing costs.

Pittsburgh Sleep Quality Index (PSQI): is a self-rated questionnaire to measure sleep quality and disturbance over 1 month. It is based on 19 items which generate a global score, ranging between 0 and 21, and 7 component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Scores above 5 signifies a poor sleeper. It is a reliable and valid measurement tool and internal consistency is acceptable in breast cancer population (Cronbach's alpha = 0.80).

Insomnia Severity Index (ISI): is a questionnaire to detect cases of insomnia and asses the insomnia severity of both night-time and daytime components of insomnia. It is based on 7 items measured on a 5-point Likert scale (0-4) which generates a total score ranging from 0 (no insomnia) to 28 (great insomnia severity). The cut-off score of 10 is optimal for detecting insomnia cases and a change score of -8.4 points is associated with a moderate improvement. ISI is a valid and reliable instrument in cancer patients and had an adequate concurrent validity of (r = 0,65).

Fatigue Severity Scale (FSS): is used to evaluate global fatigue severity in a number of chronic medical conditions such as palliative cancer. It is a short questionnaire with 9-items and the total score ranges between 9 (no fatigue) and 63 (maximum fatigue). The FSS is a reliable and valid measurement in cancer patients. The internal consistency of the FSS is highly acceptable (Cronbach's alpha = 0.96).

Pain Catastrophizing Scale (PCS): is a self-reported questionnaire to assess catastrophic thoughts or feelings accompanying the previously experienced pain. It is a 13-item measure that evaluates 3 subscales of catastrophizing: rumination, magnification and helplessness on a 5-point Likert scale. This scale ranges from 0 (not at all) to 4 (all the time) with a total score between 0 and 52. The PCS factor scales are valid and reliable.

Brief Illness Perceptions Questionnaire-Dutch Language Version (Brief IPQ-DLV): measures five illness perceptions and consists nine items. Five items assess cognitive illness (consequences, personal control, treatment control and identity), two items assess emotional perceptions (concern and emotions), one item assesses illness comprehensibility and one item assesses causal perception. The first eight items are rated on a 10-point Likert scale and the ninth item is rated as an open-ended question which asks to list three most important causal factors in the illness. The Brief IPQ-DLV has acceptable psychometric properties. The Smallest Detectable Change (SDC) is 3 point for item 1 to 8.

Pain Vigilance and Awareness Questionnaire (PVAQ): is designed to consider behaviour over the last 2 weeks in chronic pain patients. It consists 16-items that assesses attention to pain. The frequency of each item is rated on a 6-point Likert scale ranging from 0 (never) to 5 (always) with a total score ranges between 0 and 90. The higher the score, the more suggestive for a higher degree of vigilance and awareness to pain. It is highly correlated with pain-related measures such as catastrophizing, and weakly correlated with measures of unrelated constructs, such as trait anxiety. The PVAQ is a reliable and valid measurement in chronic patients.

Depression, Anxiety, Stress Scale 21 items (DASS-21): is an instrument that is used to assess anxiety and depression. Twenty-one items are subdivided in 3 categories: depression (7 items), anxiety (7 items) and stress (7 items). Each item is scored on a 4-point Likert scale ranging from 0 (not at all) to 3 (most of the time). The higher the item score, the more severe symptom of psychological distress is identified. The total score, used for the interpretation, is the sum of all items multiplied by two. The DASS-21 is a valid and reliable assessment tool in cancer patients.

State-Trait Anger Expression Inventory-II (STAXI-II): is a self-reported 57-item questionnaire that assesses the level and frequency of anger experience, expression and control. It consists three parts: (a) how angry the examinee currently feels, (b) how angry the examinee generally feels, and (c) how the examinee reacts when angry. Every item in each subscale is assessed on a 4-point Likert-scale. The validity and reliability of the STAXI-II questionnaire are satisfactory supported.

Acceptance and Action Questionnaire - II (AAQ-II): is a self-reported 7-item questionnaire that assesses the amount of acceptance and experiential avoidance, or its opposite: psychological flexibility. Every item is a statement that is scored on a 7-point Likert-scale in which one can indicate to what extent these are applicable. The higher the total score, the lower the acceptance and the higher the experiential avoidance. The psychometric qualities of the Dutch translation of the AAQ-II are good with an internal reliability of 0.87 and a construct validity of -0.67 to -0.79 for oppression and psychological complaints.

Patients' attendance at treatment sessions will be recorded. Patient adherence for the treatment sessions will be calculated as the ratio of the number of treatment sessions that were actually carried out versus the number of prescribed sessions. For the home sessions (incl. working with the information leaflet), patients will be asked to record the sessions' content in a personal log book. Treatment adherence will be calculated as a ratio of the number of sessions that were actually carried out at home versus the total number of prescribed home sessions. Patient drop-out and the reason for withdrawal will be registered.

Co-interventions will be closely monitored. Medical consumption, including the type, dose, method of administration and frequency of medication, as well as any other interventions will be recorded.

Personal characteristics including date of birth, nationality, race/ethnicity, level of education, professional situation, family income, relationship status, physical activity, smoking status, alcohol consumption, Body Mass Index (BMI), comorbidities, lymphedema, type of surgery, hormone therapy, chemotherapy, radiotherapy, immunotherapy, time since onset of complaints, time since complement of treatment, and treatment expectations will be collected at baseline.

Participants will be excluded if they are suffering from dementia or cognitive impairment (unable to understand the test instructions and/or a result of ≤11, corresponding with MMSE ≤23, on the Six-item Cognitive Impairment Test (6-item CIT) is a short questionnaire containing 6 items.

The Brief Pain Inventory is a 14-item questionnaire assessing worst pain, pain severity, and pain interference in cancer patients over the past week, reported on a scale of 0 to 10. Pain interference is measured as the average of the 7 interference items, such as walking, mood, and sleep. The Brief Pain Inventory is the most common, reliable and valid outcome measure to assess pain in cancer survivors (Cronbach's alfa and test-retest reliability score \> 0.80).

The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is a 30-item cancer-specific questionnaire developed for the assessment of quality of life in cancer patients. The EORTC QLQ-C30 is widely used in cancer studies, has been translated and validated in over 100 languages and shows acceptable psychometric properties. The internal consistence measured by Cronbach's resulted in 0.94.

The 12-item Injustice Experience Questionnaire (IEQ) will be used to assess perceived injustice. Participants have to rate the frequency of 12 different pain-related statements on a 5-point Likert scale ranging from 0 (not at all) to 4 (all the time). The sum of all items gives the total score which ranges from 0 to 48. The cut off score of 19 is suggestive for a clinically relevant case of perceived injustice.

This questionnaire obtains two correlated factors: severity/irreparability of loss and blame/unfairness. The Dutch version of the IEQ has good (test-retest) reliability (ICC = 0.86-0.87). The scores obtained using the IEQ are valid.

Medical consumption, the type, dose, method of administration and frequency of analgesic, NSAID or symptom-modifying medication, as well as surgeries will be recorded. Health care use will be evaluated using the combination of three questionnaires (online):

1. the Medical Consumption Questionnaire (MCQ)
2. the Productivity Cost Questionnaire (PCQ)
3. the EuroQol EQ-5D

The combination of these questionnaires is advised by the Institute for Medical Technology Assessment, Erasmus University Rotterdam (the Netherlands).

Vrije Universiteit Brussel

Kom Op Tegen Kanker

Hasselt University

Universitair Ziekenhuis Brussel

Pain Neuroscience Education; Four sessions of education will be applied. The neurophysiology of pain and the ability of the nervous system to modulate the experience of pain will be explained to the patient.

Standard Physiotherapy Program; Soft tissue mobilization will be applied to the upper extremity twice a week for 6 weeks.

Upper extremity exercises including breathing, warming, stretching and strengthening will be performed twice a week for 6 weeks.

Biomedical Pain Education; 4 sessions of education will be applied in 6 weeks. Pain will be explained to the patient from a biological point of view.

Standard Physiotherapy Program; Soft tissue mobilization will be applied to the upper extremity twice a week for 6 weeks.

Upper extremity exercises including breathing, warming, stretching and strengthening will be performed twice a week for 6 weeks.

Four sessions of Pain Neuroscience Education will be applied. The neurophysiology of pain and the ability of the nervous system to modulate the experience of pain will be explained to the patient.

Pain Neuroscience Education

4 sessions of Biomedical Pain Education will be applied in 6 weeks. Pain will be explained to the patient from a biological point of view.

Biomedical Pain Education

Soft tissue mobilization will be applied to the upper extremity twice a week for 6 weeks. Upper extremity exercises including breathing, warming, stretching and strengthening will be performed twice a week for 6 weeks.

Standard Physiotherapy Program

Ceren Gürşen, PhD

Rumeysa Konokman

Serap Kaya, PhD

Türkan Akbayrak, PhD

Sercan Aksoy, PhD

Yahya Doğan, MsC

Gülbala Nakip, MsC

Breast cancer is the most common type of cancer among women worldwide. Various side effects are seen after the treatments (surgery, chemotherapy, radiotherapy, etc.). Fatigue and pain are the most common and persistent side effects of breast cancer treatments. Pain management in patients currently undergoing breast cancer surgery: It consists of medical treatment, physiotherapy program and psychosocial practices. Psychosocial practices include educational interventions. The most widely used is Biomedical Education. Biomedical Education explains pain to the patient from a biological point of view and may be insufficient in curing and preventing chronic pain. The increase in the knowledge of pain physiology has revealed the modern neuroscience-based Pain Neuroscience Education. Pain Neuroscience Education explains the neurophysiology of pain and the ability of the nervous system to modulate the experience of pain. When we look at the literature, it has been seen that the lack of studies in which my Pain Neuroscience Education was applied in chronic pain after breast cancer surgery and the results of existing studies were contradictory. The aim of this study to compare the effects of Pain Neuroscience Education applied together with a standard physiotherapy program on pain, somatode function, psychological function and quality of life in patients with chronic pain after breast cancer surgery in a randomized desing. The hypotheses of this study are as follows; H1(1): The effect of Pain Neuroscience Education and Biomedical Education applied in addition to standard physiotherapy on pain-related outcomes (pain severity and disability) is different in patients with chronic pain after breast cancer surgery.

H1(2): The effect of Pain Neuroscience Education and Biomedical Education applied in addition to standard physiotherapy on somatosensory function (pressure pain threshold and mechanical perception threshold) is different in patients with chronic pain after breast cancer surgery. H1(3) : The effect of Pain Neuroscience Education and Biomedical Education applied in addition to standard physiotherapy on psychological state (psychological symptoms (stress, anxiety and depression), pain-related catastrophe) in patients with chronic pain after breast cancer surgery is different. H1(4) : Pain Neuroscience Education and Biomedical Education applied in addition to standard physiotherapy have different effects on quality of life in patients with chronic pain after breast cancer surgery. The patients were over the age of 18, diagnosed with breast cancer, had at least three months after primary cancer treatments (surgery, chemotherapy, radiotherapy), had pain in the upper extremity and shoulder region for more than three months, and were evaluated on the Visual Analogue Scale in terms of pain intensity in the last week. Patients who indicate at least 40 points out of 100 (VAS) will be included. The Mini Mental Test will be applied to individuals over 65 years of age in terms of cooperation suitability and those with a score of 24 and above will be included in the study. Cases who met the inclusion criteria and accepted to participate in the study will be randomly assigned to 2 separate groups according to the online computer-based block randomization list. Pain Neuroscience Education and standard physiotherapy program (soft tissue mobilization + exercise) will be applied to the individuals in the 1st group, and Biomedical Education and standard physiotherapy program (soft tissue mobilization + exercise) will be applied to the individuals in the 2nd group. The working period is 6 weeks. Individuals in the 1st group will receive 4 sessions of Pain Neuroscience Training, and 4 sessions of Biomedical Pain Training will be applied to the individuals in the 2nd group. Standard physiotherapy will be applied to the cases in both groups for 6 weeks, 2 sessions per week. In the first session of the treatment, individuals in both groups will be informed about the treatment process. Individuals will be evaluated in terms of research and outcome measurements twice, at the beginning of the study and at the end of the 6th week, in line with the control frequencies used routinely in the clinic. The assessment will take approximately 45 minutes for each individual. At the beginning of the study, demographic and physical characteristics of individuals, medical and surgical background (cancer history, treatments, number of sessions and/or cures), drugs used (type and dosage), and lifestyle characteristics (alcohol and smoking and regular physical activity/exercise habits) ) related information will be saved. In the evaluation; Visual Analogue Scale, Pain Disability Index, Digital Pressure Algometer, Semmes Weinstein Monoflames, Pain Disaster Scale, Depression, Anxiety-Stress Scale-21(DASS-21), Functional Assessment of Cancer Treatment-Breast ( FACT-B+4) scale will be used.

Investigation of the Efficiency of Pain Neuroscience Education in Patients With Chronic Pain After Breast Cancer Surgery

In our study, Visual Analog Scale(VAS) will be used to measure subjectively perceived pain. The Visual Analogue Scale (VAS) is a horizontal line of 0-10 cm denoting the absence of pain at one end and the most severe pain possible at the other. The subjects will be asked to mark the pain they have experienced in the last 3 days on the VAS.

Pain Disability Questionnaire (PDQ) will be used to measure pain-related disability. The Pain Disability Questionnaire (PDQ) is a seven-item scale aiming to determine the functional losses related to the musculoskeletal system suffered by the patient due to pain. From the patient, by giving 0 to 10 points to all questions; are asked to rate the impact on daily living activities, including family-home responsibilities, leisure activities, occupation, social activities, sexuality, and self-care.

The total score ranges from 0 to 70. If the result is over 40 points, it means high disability.

A Digital Pressure Algometer will be used to evaluate the pressure pain threshold. Pressure pain threshold is the amount of pressure at which pressure perception is first perceived as painful. It is applied until the participant states the point where the pressure is perceived as painful for the first time by saying 'stop'. The average of the two measurements is taken. The pressure pain threshold will be evaluated at the points in the pectoral muscle region, the lateral trunk side, and the upper trapezius muscle.

Semmes Weinstein Monofilaments will be used. The mechanical sensing threshold and the mechanical pain threshold will be measured. The mechanical sensing threshold is the point at which the stimulus is first felt. The mechanical pain threshold is the point at which the stimulus is first felt painful. It will be applied to the inner side of the upper arm, the lateral trunk side and the quadriceps muscle.

The Pain Catastrophizing Scale (PCS) will be used to measure pain-related catastrophication. This scale is a 14-item scale developed to examine catastrophic factors such as rumination, magnification, and weakness that are effective in the mechanism of pain.

PCS scores range from 0 to 52 points. It is understood that the higher the score, the higher the catastrophization.

Psychological Symptoms will be measured using the Depression Anxiety-Stress Scale-21(DASS-21). This scale measures the level of depression, anxiety and stress. It consists of 21 items and seven items in each subscale.

Functional Assesment of Cancer Treatment (FACT-B+4) Scale Coster et al. to evaluate the effects of arm morbidity on quality of life after breast cancer surgery. It consists of 42 items and 6 subscales: physical well-being, social/family well-being, emotional well-being, functional well-being, breast cancer and arm.

Hacettepe University

Doc. Dr.

Behaviors and Mental Disorders

Quality of Life

Participants will receive a 3-month online physiotherapy program comprised of 'pain neuroscience education' (month 1) and 'gradual exposure to movement' (month 2 and 3). They will receive an informative booklet online.

Participants will receive the 'usual care'. They will receive an informative booklet online and the possibility of receiving the therapeutic program, once the study is completed.

Online group therapeutic program (small groups), applied for 3 months.

Online physiotherapy protocol based on pain neuroscience education and gradual exposure to movement.

Patricia Martínez Miranda

Introduction: Pain stands out among the sequelae that affect the quality of life of breast cancer survivors. Pain neuroscience education and graded exposure to movement are therapeutic approaches that have been shown to be effective in the management of chronic pain in other populations. However, there are no previous studies that combine them in this population. Objective: To evaluate the effectiveness of an online physiotherapy focused-person program which combines pain neuroscience education and graded exposure to movement, to improve the quality of life of breast cancer survivors. Methodology: The design of the study is a randomised controlled clinical trial and the sample will be 40 breast cancer survivors with pain in the last 6 months. A random method will be used to assign participants into two groups (experimental and control). The evaluator and statistician will be blinded to participant allocation while the experimental group will receive the therapeutic program which combines pain neuroscience education and graded exposure to movement-based intervention throughout therapeutic yoga; the control will be a passive group. There will be four points of assessment: the main outcome assessed will be quality of life measured by the Functional Assessment of Cancer Therapy - Breast (FACT-B+4) and the secondary outcomes are variables related to pain experience (catastrophising, self-efficacy, kinesiophobia and fear-avoidance behaviours). All will be assessed using validated methods. SPSS program will be used for the data analysis. A mixed-model analyses of variance ANOVA (2x4) will be used to study the effects of the treatment on the dependent variables. An intention-to-treat analysis will be performed. All statistical tests will be performed considering a confidence interval of 95%. Trial record: NCT04965909.

Study Design A randomised controlled clinical trial will be carried out according to the Consolidated Standards of Reporting Trials (CONSORT) Statement for its development. In addition, the Template for Intervention, Description and Replication Checklist (TIDieR) will be used as a guide to provide transparency and make the intervention replicable. Also, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) was followed to develop this protocol. The protocol of this study has been registered on clinicaltrials.org with the registry number: NCT04965909.

Sampling method and sample's size calculation For sampling, non-probabilistic convenience and snowball methods will be used. Sample size was calculated using the G\*Power software, version 3.1.9.7 (Heinrich-Heine University, Düsseldorf, Germany), and considering the previous data reported by Park et al., (2012) for the variable global Quality of life (Functional Assessment of Cancer Therapy - Breast, FACT-B). We considered 2 groups and 4 measurements, a type I risk or α 0.05, type II risk or β 0.20 (study power of 80%), and a partial Eta2 effect size of 0.049. This generated a sample of 40 individuals, including an estimated 15% dropout rate. Figure 1 shows the study flow diagram.

Subjects' recruitment The sample for this study will be recruited through the dissemination of the project using social networks and with the collaboration of three Spanish breast carcer survivor support associations (Amama Sevilla, AGAMAMA and ASAMMA). Participation in the study will be voluntary. All participants will be facilitated by written informed consent that must be signed to be part of the clinical trial.

Group assignment and masking This study will have two groups (experimental and control). For assignment, a random method will be carried out using an online tool called 'random allocation software'. A stratified allocation was applied according to the women's age (≤45 years old or \>45 years old). On each of the strata, a randomisation will be carried out by blocks of constant size. The assignment sequence will be hidden from the evaluator and the study subjects through an automated assignment system. The preparation of the sequence, the inclusion of the individuals in each group and the assignment of the treatments will be carried out by different members of the research team. On the other hand, the evaluator and statistician will be blinded. Nonetheless, the therapist and subject will not be able to be blinded because of the type of intervention.

Assessment points, method of data collection and outcomes The outcomes will be assessed at four points during the entire study period: before the intervention (T0), after the experimental group completes the first part of the intervention based on PNE (T1), after complete intervention (T2) and at the 3-month follow-up (T3) (Figure 2).

All data will be collected in a format model. All data were encrypted and only members of the research team will have access to the data of the participants. The outcomes will be assessed using validated scales or questionnaires that women will complete by themselves. In addition, extra information related to their pain context will be collected by two evaluators in an online meeting. The evaluators will have previous experience in the issue and will be trained before the interviews.

The main outcome of this trial is quality of life measured by The Functional Assessment of Cancer Therapy - Breast (FACT-B+4). In addition, five secondary outcomes related to health will be measured: intensity of pain using the Brief Pain Inventory - Short Form (BPI-SF), catastrophising level using the Pain Catastrophising Scale, self-efficacy level using the Pain Self-efficacy questionnaire (PSEQ), Kinesiophobia using the Tampa Scale for Kinesiophobia (TSK-11) and fear-avoidance behaviours using the Fear Avoidance Components Scale Questionnaire - Spanish Version (FACS-SP).

Method for results and data analysis For the data analysis, a data matrix will be prepared according to the coding methods that have been described in the outcomes section. A descriptive and inferential statistical analysis will be carried out, assuming that the groups are independent. The SPSS program, version 26.0 for Windows will be used for data analysis.

First, the Shapiro-Wilk test will be used to determine whether there is a normal distribution. Then, a descriptive analysis of the data will be conducted. The absolute count and percentages of each category will be calculated in the nominal qualitative variables. For the quantitative variables adjusted to the normality, the mean and standard deviation will be provided, while the median and the first and third quartiles will be provided in those that are not adjusted to normality. Next, the homogeneity in the baseline between the experimental and control groups will be studied with respect to the sociodemographic and clinical variables and pre-test of all dependent variables. In the dichotomous nominal qualitative variables, Pearson's bilateral asymptotic Chi2 test will be used, or, failing that, Fisher's exact test. In the polytomous nominal qualitative variables, Pearson's bilateral asymptotic Chi2 test or Pearson's exact test will be used. On the other hand, in the quantitative variables adjusted to normality that are homoscedastic, we will use the student's t test for independent samples and the Welch t test in those that are heteroscedastic. In quantitative variables that do not adjust to normality, the Mann-Whitney U test will be used. On the other hand, in those variables in which the 4 measurements are adjusted to normality in both intervention groups, a mixed-model analyses of variance factorial ANOVA (2x4) will be used to study the effects of the treatment on the dependent variables evaluated in the present investigation, considering the group as a between-subject factor and time (the different measurements performed) as a within-subject factor. The hypothesis of interest will be the interaction group by time with an a priori alpha level of 0.05. In addition, the effect size of the observed differences will be estimated by calculating the partial Eta squared coefficient. In those variables in which none of the measurements in either of the two intervention groups adjust to normality, the following analyses will be implemented: the measurements made of the intragroup dependent variables will be compared (considering each of the intervention groups in isolation). In those variables in which all of the measurements are normal in one of the two intervention groups, we will use the ANOVA test of repeated measures. If any of the measurements do not adjust to normality, we will use the Friedman ANOVA test. Next, to compare the inter-group dependent variables, the difference between the value of each pair of measurements will be calculated for each dependent variable, calling such values "differences". In addition, the percentages of change in the scores between each pair of measurements were established. Finally, the values obtained in the "differences in scores" and in the "percentage changes in scores" in the two groups will be compared. For this we use Student's t test for independent samples, in the differences and percentages of change that are normal and homoscedastic, while in the normal and heteroscedastic we will use the Welch t test. The effect size was estimated by calculating Cohen's d coefficient. In the event that such differences are not normal, we will used the Mann-Whitney U test and the effect size will be found by calculating Rosenthal's r with the formula: r=Z/√N. An "intention to treat" analysis will be performed in the study of the effects of the applied intervention. All statistical tests will be performed considering a confidence interval (hereinafter CI) of 95% (p-value \<0.05).

Planned timing The project would be carried out from 2020 to 2024.

Ethical considerations For the preparation of this study, all relevant ethical considerations have been made. In addition, this program has the approval of the Research Ethics Committee (CEI) of the Virgen Macarena - Virgen del Rocío University Hospitals.

In accordance with Organic Law 3/2018, of December 5, on the Protection of Personal Data and guarantee of digital rights and prior verbal and written information, this study will have the express written consent of each participant. This will be delivered together with the informed consent revocation sheet. All personal data will be treated properly, not being disclosed under any circumstances and not being misused.

A Randomized Controlled Clinical Trial of two groups (experimental and control) will be carried out.

double-blind (researcher and statistician)

Pain Neuroscience Education and Graded Exposure to Movement in Breast Cancer Survivors

Online Pain Neuroscience Education and Graded Exposure to Movement in Breast Cancer Survivors: Protocol of a Randomised Controlled Trial.

The personal data of the participants will be treated in accordance with the Organic Law 3/2018, of December 5, on the Protection of Personal Data and guarantee of digital rights

Quality of life measured by the Functional Assessment of Cancer Therapy - Breast (FACT-B+4). The FACT-B+4 is a 41-item instrument designed to measure six domains of QOL in breast cancer patients: Physical, social, emotional and functional well-being, and breast-cancer (BCS) and lymphedema (ARM) subscales. The score obtained ranges from 0-148 points. The ARM subscale was not included in the total score. A higher score translates into a better quality of life.

Pain intensity measured by the Brief Pain Inventory - Short Form (BPI - SF). The PBI -SF is a 9-item instrument designed to measure pain intensity and pain interference with the diary daily activities. The questionnaire has two subareas, one related to pain intensity, whose score ranges from 0-50, with a higher score being an indication of greater intensity; and another related to the interference of pain in activities of daily living, whose score ranges from 0-70, with a higher score being indicative of a greater impact on daily life.

Catastrophim level measured by the Pain Catastrophizing Scale. This scale allows us to assess the degree of catastrophizing of pain in adolescents and adults who face this condition as a result of various pathologies or diseases. The scale consists of 3 subscales (rumination, magnification and helplessness), whose items will be valued from 0 (nothing) to 4 (all the time) to obtain a total score that ranges between 0-52. A higher score translates into a higher level of catastrophizing.

Self-efficacy level measured by the pain self-efficacy questionnaire (PSEQ). The PSEQ is a 22-item instrument designed to measure self-efficacy level. Each item is scored from 0 - 10. 0 is equal to 'I think I am totally incapable' and 10 is equal to 'I think I am totally capable'. The total score ranges from 0-220. A higher score on the questionnaire corresponds to a higher level of self-efficacy.

Kinesiophobia measured by the Tampa Scale for Kinesiophobia (TSK-11). This scale is one of the most used to evaluate kinesiophobia in patients with pain. It is composed of two factors (avoidance of activity and harm) with a total of 11 items that are valued from 1 (totally disagree) to 4 (totally agree). The total score obtained ranges from 11 - 44. More punctuation shows higher kinesiophobia level.

Fear avoidance beliefs measured by the Fear Avoidance Components Scale Questionnaire - Spanish Version (FACS - SP) . The FACS- SP is a questionnaire that allows us to evaluate patient's fear of pain and consequent avoidance of physical activity due to fear. The questionnaire consists of 20 items in which a patient rates his agreement with each statement on a 6-point Likert scale. Where 0 = completely disagree, 6 = completely agree. There is a maximum score of 100. A higher score indicates more strongly held fear-avoidance beliefs. Five severity levels are available for clinical interpretation: subclinical (0-20), mild (21-40), moderate (41-60), severe (61-80), and extreme (81-100).

University of Seville

Doctoranda Programa del Doctorado Interuniversitario en CCSS

Cancer Pain

This consists of generating elements from neurobiology and neurophysiology for the understanding of pain from the development of metaphors.

Pharmacological treatment and indications estimated by a specialist in palliative care and pain.

PNE sessions will be led by an experienced physical therapist certified in PNE in 35-minute face-to-face group sessions. Here elements of the neurophysiology of pain are addressed, as well as the different psychosocial dimensions that influence it. The distribution of themes will be carried out as follows:

Week One: Coping with Pain. Week 2: Pain and Cognition Week 3: Your security system Week 4: Altered Alarm System (extra sensitive). Week 5: The defense system is in distress. Week 6: Fatigue, anxiety, and stress Week 7: Current Models of Treatment Week 8: Achievements and goals Week 9: Pain emphasis and differentiation This group remains with pharmacological treatment and the usual guidelines given by the doctor.

Pain neuroscience education

This group will only have pharmacological treatment and the usual guidelines given by the doctor. Without educational intervention.

Conventional management or Usual care

Leidy Tatiana Ordoñez-Mora, MSC

Leidy Tatiana Ordoñez-Mora

Ilem Dayana Rosero-Rosero, PhD

Juan Carlos Avila Valencia, MSC

Juan Carlos Avila-Valencia, MSC

Julian Alberto Agudelo, MSC

IASP defines "pain" as "an unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage". In some patients, pain is one of the reasons they initially consult a doctor and will be strongly related to cancer itself, is connected to receiving the cancer diagnosis, and therefore may become an uncertain threat of disease recurrence in cancer survivors. Neuropathic pain is the most prevalent type of pain, but a mixed type of pain is also common, reflecting the complexity of the pain experience. There is increasing evidence in oncology that quality of life and survival are linked to early and effective palliative care, including pain management. Although improvements have been seen, undertreatment of pain remains a problem in a significant subset of cancer patients. Regarding the interventional options in cancer pain, multiple possibilities range from pharmacological modulation, the use of modalities or physical means, as well as the practice of physical exercise as a mechanism of pain modulation, which has been established according to the background grade of recommendation. Regarding education in neuroscience, this has gained momentum in chronic pain since previous interventions have generated recommendations to include neurocognitive interventions in pain processes. Therefore, it seeks to determine the effectiveness of a neuroscience education program compared to conventional treatment in adults with cancer pain in biopsychosocial variables.

A parallel group randomized controlled clinical trial will be conducted during the months of November 2022 to December 2023. The proposed research will be a quantitative experimental design type controlled clinical trial following the SPIRIT guidelines for clinical trial protocols and CONSORT for the execution of clinical trials.

A total of 80 patients, where 40 will be assigned to (PNE) and 40 to conventional management. experimental group: based on education in neuroscience of pain for 9 sessions in a period of 10 weeks. Work will be done to prepare the content for an adapted and illustrated guide as a complementary material for patients. An expert judgment test will be carried out to validate the content of the material. Each patient must complete at least 8 sessions to comply with the protocol. These sessions will be personalized and will include the guide as complementary material for each session. This group remains with pharmacological treatment and the usual guidelines given by the doctor. Results will be assessed at baseline (t1) and at week 10 (t2). Written informed consent will be obtained from all participants prior to their participation.

Parallel Assignment Masking: Simple (result evaluator)

Effectiveness of a Pain Neuroscience Education Program in Adults With Cancer Pain

The Effectiveness of a Pain Neuroscience Education Program Compared to Conventional Treatment on Pain, Biopsychosocial Variables, and Functional Capacity in Adults With Cancer Pain

It is performed to determine exercise tolerance and specify functional status. This evaluates the number of meters traveled during the last 6 minutes.

It is a marker of nutritional status and a marker of morbidity and mortality of the pathology. It will be measured with a dynamometer to establish the grip strength value in kilograms.

This test has been developed, finding that it has been a predictor of falls and as a measure of functional capacity. n this test, the participant starts in a chair, stands up, runs three meters, and sits down again. The time of the execution of the test is taken.

The BPI or brief pain questionnaire is a self-administered questionnaire that contains two dimensions: one related to the intensity of pain and the impact of pain on the activities of the patient's life. Its use has increased in the evaluation of patients with cancer pain. The patient is asked to rate their worst, least, average, and current pain intensity, list current treatments and their perceived effectiveness, and rate the degree that pain interferes with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life on a 10 point scale. the higher the score, the greater the severity of the pain.

The severity of the pain at rest was assessed on a 10 cm visual analog scale (Total score: 0-10)(0=no pain, 10=severe pain) Higher scores mean a worse outcome.

Central Sensitization Inventory (CSI) is a scale used to detect patients with symptoms associated with central sensitization or types of central sensitization syndrome such as fibromyalgia, temporomandibular joint disease, tension type headache, migraine.

The Central Sensitization Inventory (CSI) consists of two parts:

Part A consists of 25 questions about central sensitization syndrome (CNS) symptoms; Section B examines the patient's condition of being diagnosed with certain CNS diseases or CNS related diseases such as anxiety and depression.

The patient answers 25 questions in section A with a score between 0 and 4. The total score will be between 0-100. Results above 40 points indicate central sensitization.

The PCS is measured with a self-administered questionnaire. Is a 13-item inventory that measures 3 elements of the perception of the intensity of pain (rumination, magnification, feeling helpless). Participants indicate the degree to which they agree with statements related their pain by selecting 0 = not at all, 1 = to a slight degree, 2 = to a moderate degree, 3 = to a great degree, 4 = all the time. There are three subscale scores assessing rumination, magnification and helplessness. All subscales are summed to produce a total score ranging from 0 to 52 with higher scores indicating the participant is having more thoughts about the pain they feel helplessness. All subscales are summed to produce a total score ranging from 0 to 52 with higher scores indicating the participant is having more thoughts about the pain they feel.

TSK-11 is used to assess fear of pain and movement. It consists of 11 items, which are answered on a Likert scale of 4 points. Total scores of each scale range from 11 to 44, where higher scores indicate a greater fear of pain and movement.

Beck Depression Criterion (BDI) is a commonly used evaluation criterion for diagnosis and follow-up parameters in assessing depression status.It contains 21 categories to measure physical, emotional, cognitive and motivational symptoms such as hopelessness, irritability, guilt, feeling of punishment, fatigue, and weight loss in each depression, and each category is scored between 0-3. The patient is asked to mark the most appropriate one for the four options in each category. Scoring progressively increases from the absence of symptoms to severe symptoms. 0-10 points: No depression, 11-17 points: Mild depression, 18-23 points: Moderate depression, 24 and above points: Severe depression.

We will work with the DN4 scale that evaluates 4 questions with a possibility of being qualified up to 10 points to determine the presence of neuropathic pain.

It is made up of 19 items and eight cognitive domains that assess skills such as visuospatial/executive, naming, memory, attention, language, abstraction, delayed recall, and orientation. a maximum score of 30, with the cut-off points for cognitive impairment being 25/26.

has been defined as the way in which the individual perceives his/her place in life, The standard model consists of 14 domains and an empirical solution with five domains (physical, psychological, frailty, socioeconomic, and global score). This widely used questionnaire consists of five functional scales (physical, role, cognitive, emotional, and social function), a global quality of life (QoL) scale, three symptom scales (fatigue, nausea and vomiting, and pain), and six individual. items (loss of appetite, diarrhea, dyspnea, constipation, insomnia, economic impact). For the functional and global quality of life scales, a higher score indicates better health. For the symptom scales, a higher score indicates a higher symptom burden.

This is one of the most reliable tests to define the quality of sleep and its disorders. It contains a total of 19 questions, grouped into 10 questions. The questions are combined to form seven areas with their corresponding score, each one of which shows a range between 0 and 3 points.

Universidad Santiago de Cali

Clinica de Occidente

Instituto Neurociencia Del Dolor

Kinesiophobia

Phobic Disorders

Anxiety Disorders

Mental Disorders

Psychotic Disorders

Participants will receive a 9-week physiotherapy program. Consisting of 3 sessions of pain neuroscience education and 24 sessions of therapeutic exercise (16 face-to-face sessions and 8 at home).

Pain neuroscience education and therapeutic exercise

Jose Antonio Lores, PT

Introduction: Breast cancer represents the most common type of malignant neoplasm worldwide. Advances in diagnosis and treatment have increased the life expectancy of patients. However, the sequelae associated with treatment and disease in survivors such as chronic pain, kinesiophobia and loss of physical function represent a long-term health problem. Physical therapy is a frequently used strategy for the treatment of sequelae in the acute stage of the disease, but there is a need to evaluate its effectiveness in cancer survivors with chronic sequelae. Therapeutic exercise and pain neuroscience education have been shown to be effective in the management of populations with chronic pain and loss of function; however, more evidence is needed in specific populations of cancer survivors. Objective:To evaluate the effectiveness of a physical therapy program based on pain neuroscience education and therapeutic exercise for the treatment of chronic pain, kinesiophobia and loss of physical function in breast cancer survivors. Methodology. Quasi-experimental study. The sample will consist of 40 female breast cancer survivors. The intervention will last 9 weeks, with 3 sessions of pain neuroscience education and 24 sessions of therapeutic exercise, 3 times per week (16 face-to-face sessions and 8 sessions at home). The intervention will be carried out in small groups of 8 to 12 people. The frequency and intensity of pain, the level of kinesiophobia and physical functionality and the range of of motion of the shoulder will be evaluated in 4 assessments, before the intervention (T0), 3rd (T1), 6th (T2) and 9th (T3) week of the intervention. Different validated measurement instruments will be used in this population such as self-report scales, questionnaires and the use of a goniometer.

Pain Neuroscience Education and Therapeutic Exercise as a Treatment for Breast Cancer Survivors Living With Sequelae

Pain Neuroscience Education and Therapeutic Exercise as a Treatment for Chronic Pain, Kinesiophobia and Increased Physical Functionality in Breast Cancer Survivors

An initial survey with 2 sections will be applied: the first will collect information on sociodemographic variables such as: age, marital status, occupation, level of schooling, weight, height, BMI, habits (alcohol and tobacco) and comorbidities. The second will contain questions on the clinical characteristics of breast cancer such as: number of months with pain, time since initial diagnosis, time elapsed and stage of breast cancer at diagnosis, type of breast cancer according to histological classification, hormone receptor status, location of breast cancer (right, left or bilateral), type of surgery and other treatments (radiotherapy, chemotherapy, hormone therapy or inmunotherapy), the region of pain (axilla, shoulder, arm or thorax).

The DN4 questionnarie will be used to discriminate between neuropathic and nociceptive type of pain. The DN4 questionnaire consists of a total of 10 items grouped in 4 sections. The first seven items are related to the quality of pain (burning, painful cold, electric shocks) and its association to abnormal sensations (tingling, pins and needles, numbness, itching). The other 3 items are related to neurological examination in the painful area (touch hypoesthesia, pinprick hypoesthesia, tactile allodynia). A score of 1 is given to each positive item and a score of 0 to each negative item. The total score is calculated as the sum of all 10 items, and the cut-off value for the diagnosis of neuropathic pain is a total score of 4/10.

To evaluate central sensitization related symptoms part A of the Spanish Central Sensitization Inventory (CSI) will be used. Part A of the CSI assesses 25 health-related symptoms common to central sensitization, with total scores ranging from 0 to 100. . A total score of 40 or higher indicates the presence of central sensitization.

To evaluate possible nociplastic pain, the clinical criteria for nociplastic pain affecting the musculoeskeletal system propose by the International Association for The Study of Pain (IASP) Terminology Task Force (TTF) will be used. It consists of 4 items to clinically evaluate: the type of pain (if greater than 3 months, its distribution and the presence or not of nociceptive type of pain), history of hypersensitivity in the region of pain, presence of comorbidities (sensitivity to sound or light, sleep problems, fatigue or cognitive problems), evoked pain hypersensitivity in the region of pain (static mechanical allodynia, static dynamic allodynia, allodynia to heat or cold). Presence of item 1 and 4 is classifed as possible nociplastic pain, and all of the above (item 1, 2, 3 and 4) as probable nociplastic pain.

Pain intensity will be measured using the visual analog scale (VAS), participants will report their pain intensity within a range of 0 to 100 millimeters, with 0 being no pain and 100 being the maximum pain.

Participants will report the number of days per week with pain.

Kinesiophobia will be measured through the Tampa Kinesiophobia Scale Spanish version with 11 items (TSK-11V). It consists of a self-report instrument with 11 items related to fear of movement or injury relapse. Each ítem is measured on a Likert-type scale between 1 and 4 points, being 1 totally disagree and 4 totally agree, being able to obtain a total between a range of 11 to 44 final points. The higher the score, the higher the level of kinesiophobia.

Physical functionality will be measured through the Upper Limb Functional Index scale (ULFI-Sp), which consists of a list of 25 items. Each item is scored on a 3-point scale by filling in a box, so that filling in the whole box means strongly agree, half a box means partially agree, and leaving it empty means strongly disagree, giving it a score of 1, 0.5 and 0 points respectively. The total score (25 points maximum) is multiplied by 4 to obtain a score based on 100 points, of which 0 would represent no functional limitation and 100 maximum limitation. The first 16 items refer to common functional activities, while the other 9 focus on activities involving the use of the upper limb.

Active joint range of motion (active ROM) will be measured as part of the physical function assessment of the patient's upper limb. Flexion, horizontal flexion, extension, internal rotation, external rotation and abduction of both shoulders will be measured. Active ROM will be measured using a BASELINE® brand 12-inch shoulder goniometer. Three goniometric measurements will be taken per movement, and the average will be taken to obtain a value of the active ROM between a range of 0 and 180 degrees.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PI-targeted PNE+MI Compared to BIOMEDICAL Education in BCS	NCT04730154	Breast Neoplasm... Survivorship Pain, Chronic	Pain Neuroscien... Motivational In... Biomedically-fo...	18 Years -	Universitair Ziekenhuis Brussel
Investigation of the Efficiency of Pain Neuroscience Education in Patients With Chronic Pain After Breast Cancer Surgery	NCT06052085	Breast Cancer	Pain Neuroscien... Biomedical Pain... Standard Physio...	18 Years -	Hacettepe University
Pain Neuroscience Education and Graded Exposure to Movement in Breast Cancer Survivors	NCT04965909	Breast Neoplasm... Pain, Chronic Quality of Life	Online physioth...	18 Years - 65 Years	University of Seville
Effectiveness of a Pain Neuroscience Education Program in Adults With Cancer Pain	NCT05581784	Cancer Pain	Pain neuroscien... Conventional ma...	40 Years - 75 Years	Instituto Neurociencia Del Dolor
Pain Neuroscience Education and Therapeutic Exercise as a Treatment for Breast Cancer Survivors Living With Sequelae	NCT05452499	Breast Neoplasm... Pain, Chronic Kinesiophobia Breast Cancer	Pain neuroscien...	25 Years - 65 Years	Universidad Autónoma de Yucatán

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