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Pain is a prevalent and debilitating healthcare problem. Since pharmacological treatments have numerous side-effects, additional treatment could be beneficial. Music has been shown to affect the pain perception and the pain threshold. The objective of this observational study was to evaluate the effect of preferred music as opposed to disliked music on pain (tolerance) thresholds and perceived pain intensity in healthy volunteers. Pain thresholds were measured via quantitative sensory testing. The volunteers were randomly assigned to either handheld pressure algometry to assess the pressure pain threshold to or electrical measurements to assess the electrical pain tolerance threshold while listening to preferred and disliked music. The pain thresholds were administered on the dorsal side of the forearm. The perceived pain intensity was assessed via a numerical rating scale, ranging from 0 (no pain) to 10 (worst pain imaginable). In total 415 volunteers were included in this study. The pressure pain threshold was assessed in 277 volunteers and in the electrical pain tolerance threshold test 138 volunteers were entered. In both groups, preferred music yielded higher pain thresholds than disliked music ( P <0.001) and lower perceived pain intensity during the stimulus (P = 0.003). Moreover, the highest pain thresholds of both pressure pain and electrical pain tolerance thresholds were obtained when the preferred music was preceded by disliked music. Listening to preferred music when receiving noxious stimuli leads to higher pain thresholds and lower perceived pain scores in comparison with disliked music. Preferred music could be beneficial for patients with pain or undergoing painful procedures.

Neuropathic pain is clinically described as pain caused by a lesion or disease of the somatosensory nervous system. The aim of this study was to assess the validity of the Dutch version of the DN4, in a cross-sectional multicentre design, as a screening tool for detecting a neuropathic pain component in a large consecutive, not pre-stratified on basis of the target outcome, population of patients with chronic pain. Patients' pain was classified by two independent (pain-)physicians as the gold standard. The analysis was initially performed on the outcomes of those patients (n = 228 out of 291) in whom both physicians agreed in their pain classification. Compared to the gold standard the DN4 had a sensitivity of 75% and specificity of 76%. The DN4-symptoms (seven interview items) solely resulted in a sensitivity of 70% and a specificity of 67%. For the DN4-signs (three examination items) it was respectively 75% and 75%. In conclusion, because it seems that the DN4 helps to identify a neuropathic pain component in a consecutive population of patients with chronic pain in a moderate way, a comprehensive (physical-) examination by the physician is still obligate.

Transcutaneous vagal nerve stimulation has analgesic potential and might be elicited by abdominally administered low-frequency vibrations. The objective was to study the safety and effect of a combination of music and abdominally administered low-frequency vibrations on pain intensity in elderly patients with chronic musculoskeletal pain. This trial was an international multicenter, randomized controlled pilot study. Patients at age ≥ 65 years with musculoskeletal pain for ≥ 3 months and a daily pain score ≥ 4 out of 10 were recruited at three centers. They were randomized to receive either a combination of music and low-frequency (20-100 Hz) vibrations administered to the abdomen, or a combination with the same music but with higher frequency (200-300 Hz) vibrations administered to the abdomen. Low-frequency vibrations were expected to result in pain reduction measured with a numeric pain rating scale (NRS). Patients in both groups received eight treatments of the music combined with the vibrations in three weeks. Primary outcomes were safety (Serious Adverse Events) and pain intensity measured at baseline, after the last treatment and at six weeks follow-up. Multilevel linear model analyses were performed to study group and time effects. A total of 45 patients were analyzed according to intention-to-treat principle. After 344 treatments, 1 Adverse Event was found related to the intervention, while 13 Adverse Events were possibly related. A multilevel linear model showed that the interaction effect of group by time did not predict pain intensity (F[1, 45.93] = 0.002, p = 0.97) when comparing pain intensity at baseline, after the last treatment and at follow-up. The combination of music and abdominally administered vibrations was found to be safe and well tolerated by the elderly patients. However, over time, neither the low-frequency treatment group nor the high-frequency treatment group provided clinically meaningful pain relief. There is no evidence that the low-frequency treatment elicited vagal nerve stimulation. The trial was prospectively registered in the Netherlands Trial Register (NTR: NL7606) on 21-03-2019.

The treatment-related burden for patients undergoing hematopoietic stem cell transplantation (HSCT) may be relieved by physical exercises. The purpose of this study was to summarize and analyze the evidence provided by randomized controlled trials (RCTs) on physical exercise interventions among patients with cancer undergoing HSCT. PubMed, CINAHL, EMBASE, the Cochrane Library, and PEDro were searched for relevant RCTs up to October 1, 2011. Two reviewers screened articles on inclusion criteria and indentified relevant RCTs. Two authors assessed the selected articles for risk of bias. Data extraction was performed by 1 reviewer. Meta-analyses were undertaken to estimate the outcomes quality of life (QOL), psychological well-being and distress, and fatigue. Eleven studies were included, with study populations consisting of recipients undergoing either an allogeneic or autologous HSCT (n=734). Four studies had low risk of bias. The exercise interventions were performed before, during, and after hospitalization for the HSCT. Different exercise programs on endurance, resistance and/or activities of daily living training, progressive relaxation, and stretching were used. Meta-analyses showed that exercise during hospitalization led to a higher QOL (weighted mean difference=8.72, 95% confidence interval=3.13, 14.31) and less fatigue (standardized mean difference=0.53, 95% confidence interval=0.16, 0.91) in patients with an allogeneic HSCT at the moment of discharge from the hospital. No marked effects were found for psychological well-being and distress. Individual study results suggested significant positive effects on QOL, fatigue, psychological well-being and distress, and physical functioning. Prevalent shortcomings in the included studies were the heterogeneity among studies and the lack of blinding of participants, personnel, and outcome assessment. The results suggest that recipients of HSCT may benefit from physical exercise.

Sex is an important factor influencing the development and treatment of chronic pain, but the extent of its influence is still unclear. Other demographic factors as well as nonpharmacological interventions might influence pain sensitivity differently in men and women. In this study, we aimed to investigate the influence of sex and other demographic, lifestyle, behavioral, clinical, and environmental factors on pain sensitivity in the Dutch population. Different films were used to investigate how they would impact pain sensitivity and what influence sex and other variables have on the effect of this simple intervention. We performed a study consisting of 2 parts: (1) a cross-sectional research to investigate pain sensitivity differences between men and women and the influence of other demographic variables on the pain sensitivity in a Dutch cohort and (2) an internet intervention study to determine whether a short film could skew pain sensitivity. All respondents filled in a web-based demographic questionnaire and were randomized into 4 groups. The control group filled in the Pain Sensitivity Questionnaire without watching a preliminary film. A cross-sectional analysis was performed in the control group (n=1746). The other 3 groups watched short films: one group watched a film with scenes of nature (n=2650), another group watched a film on laughing people (n=2735), and the last group watched a film on physically painful events (n=2708). Immediately after the film viewing, participants were directed to the Pain Sensitivity Questionnaire to measure their pain sensitivity. The Pain Sensitivity Questionnaire score was stated as a mean per question on the numeric rating scale from 0-1. The cross-sectional study revealed no significant differences between men and women but showed male-female differences in the Pain Sensitivity Questionnaire when specific background factors were present. Watching a short film had a positive impact on the pain sensitivity of the respondents who had chronic pain, with a higher effect observed in female respondents. Scientists performing pain research need to account for factors that can influence the outcome of their study and be aware that these factors can be sex-dependent, and pain sensitivity should be analyzed accordingly. Even relatively small interventions such as watching a film can impact pain sensitivity, especially in respondents with current chronic pain. This effect can vary as well when different background factors are present. Our findings warrant further explorations of the possibilities that simple interventions bring for patients in personalized medicine. Landelijk Trial Register NTR-new NL8182; https://onderzoekmetmensen.nl/en/trial/29537.

IntroductionPatients with chronic low back pain radiating to the leg (CLBPr) are sometimes referred to a specialised pain clinic for a precise diagnosis based, for example, on a diagnostic selective nerve root block. Possible interventions are therapeutic selective nerve root block or pulsed radiofrequency. Central pain sensitisation is not directly assessable in humans and therefore the term ‘human assumed central sensitisation’ (HACS) is proposed. The possible existence and degree of sensitisation associated with pain mechanisms assumed present in the human central nervous system, its role in the chronification of pain and its interaction with diagnostic and therapeutic interventions are largely unknown in patients with CLBPr. The aim of quantitative sensory testing (QST) is to estimate quantitatively the presence of HACS and accumulating evidence suggest that a subset of patients with CLBPr have facilitated responses to a range of QST tests.The aims of this study are to identify HACS in patients with CLBPr, to determine associations with the effect of selective nerve root blocks and compare outcomes of HACS in patients to healthy volunteers.Methods and analysisA prospective observational study including 50 patients with CLBPr. Measurements are performed before diagnostic and therapeutic nerve root block interventions and at 4 weeks follow-up. Data from patients will be compared with those of 50 sex-matched and age-matched healthy volunteers. The primary study parameters are the outcomes of QST and the Central Sensitisation Inventory. Statistical analyses to be performed will be analysis of variance.Ethics and disseminationThe Medical Research Ethics Committee of the University Medical Center Groningen, Groningen, the Netherlands, approved this study (dossier NL60439.042.17). The results will be disseminated via publications in peer-reviewed journals and at conferences.Trial registration numberNTR NL6765.

BackgroundIn many patients with axial spondyloarthritis (axSpA), pain persists despite anti-inflammatory medication. Quantitative sensory testing (QST) indirectly assesses altered somatosensory function, though its clinical practicality is limited. The Central Sensitisation Inventory (CSI) could be an alternative in the initial assessment of central sensitisation (CS). This study aimed to investigate the value of the CSI in evaluating CS in patients with axSpA by (1) assessing somatosensory function related to CS with QST and (2) exploring associations between CSI, QST, patient and disease characteristics and pain-related psychosocial factors.MethodsConsecutive outpatients from the Groningen Leeuwarden AxSpA cohort underwent QST, including pressure pain threshold (PPT), temporal summation (TS) and conditioned pain modulation (CPM). Participants completed questionnaires assessing CS (CSI), illness perception (Revised Illness Perception Questionnaire, IPQ-R), pain-related worrying (Pain Catastrophising Scale, PCS), fatigue (Modified Fatigue Impact Scale, MFIS), anxiety/depression (Hospital Anxiety and Depression Scale, HADS) and coping. QST measurements were stratified for CSI≥40.Results201 patients with axSpA were included; 63% male, 64% radiographic axSpA, median symptom duration 12 years (IQR 5–24), mean Axial Spondyloarthritis Disease Activity Score 2.1±1.0. Patients with CSI≥40 had significantly lower PPTs and higher TS than CSI<40 (p<0.004). No significant differences in CPM were observed. In multivariable linear regression, sex, PCS, IPQ-R Identity, MFIS and HADS anxiety were independently associated with CSI (78% explained variance).ConclusionIn this large cross-sectional study in patients with axSpA, the CSI appears as a useful initial CS assessment questionnaire. When CSI scores indicate CS, considering pain-related psychosocial factors is important. These results emphasise the need for a biopsychosocial approach to manage chronic pain in patients with axSpA.

Background Opioids are effective in pain-management, but long-term opioid users can develop prescription opioid use disorder (OUD). One treatment strategy in patients with OUD is rotating from a short-acting opioid to a long-acting opioid (buprenorphine/naloxone (BuNa) or methadone). Both BuNa and methadone have been shown to be effective strategies in patients with OUD reducing opioid misuse, however data on head-to-head comparison in patients with chronic non-malignant pain and prescription OUD are limited. Methods This two-armed open-label, randomized controlled trial aims to compare effectiveness between BuNa and methadone in patients with chronic non-malignant with prescription OUD (n = 100). Participants receive inpatient rotation to either BuNa or methadone with a flexible dosing regimen. The primary outcome is opioid misuse 2 months after rotation. Secondary outcomes include treatment compliance, side effects, analgesia, opioid craving, quality of life, mood symptoms, cognitive and physical functioning over 2- and 6 months follow-up. Linear mixed model analysis will be used to evaluate change in outcome parameters over time between the treatment arms. Discussion This is one of the first studies comparing buprenorphine/naloxone and methadone for treating prescription OUD in a broad patient group with chronic non-malignant pain. Results may guide future treatment for patients with chronic pain and prescription OUD. Trial registration https://www.trialregister.nl/ , NL9781

IntroductionA relevant subsample of patients with chronic low back pain (CLBP) have manifested augmented central pain processing, central sensitisation (CS). Patients with CLBP have limited functioning and participation. Theoretically, physical functioning in patients with CLBP can plausibly be linked to CS; however, evidence to explain such association is scarce. Moreover, there is no gold standard for CS diagnosis. The objectives of the study are: (1) to analyse the association between instruments assessing reference symptoms and signs attributed to CS; (2) to analyse whether reference symptoms and signs attributed to CS are associated with functioning measurement outcomes; and (3) to analyse whether changes (between baseline and discharge) in reference symptoms and signs attributed to CS are related to changes in each of the functioning measurement outcomes.Methods and analysisA cross-sectional and longitudinal observational study is performed with measurements taken at baseline and discharge of an interdisciplinary rehabilitation programme. A sample size of 110 adult patients with CLBP has been calculated for the study. CS measurements are: Central Sensitisation Inventory, quantitative sensory testing and heart rate variability. Functioning measurements are: lifting capacity, maximal aerobic capacity, accelerometry and reported functioning. Statistical analyses to be performed are: (1) correlation between CS measurements, (2) multiple regression between functioning (dependent variable) and CS measurements (independent variable), and (3) multiple regression between changes in scores of functioning (dependent variable) and CS measurements (independent variable), and corrected for sex and age.Ethics and disseminationThe study obtained the clearance to its implementation from the Medical Research Ethics Committee of the University Medical Center Groningen in July 2017. The results will be disseminated through scientific publications in peer-reviewed journals, presentations at relevant conferences, and reports to stakeholders.Trial registration numberNTR7167/NL6980.

Central sensitization cannot be directly demonstrated in humans and thus a gold standard is missing. Therefore, we used human assumed central sensitization (HACS) when associated with humans. The central sensitization inventory (CSI) is a screening questionnaire for addressing symptoms that are associated with HACS. This cross-sectional study compared patients with chronic pain and at least one central sensitivity syndrome with healthy, pain-free controls via ROC analyses. Analyses were performed for all participants together and for each sex separately. Regression analyses were performed on patients with chronic pain with and without central sensitivity syndromes. Based on 1730 patients and 250 healthy controls, cutoff values for the CSI for the total group were established at 30 points: women: 33 points; men: 25 points. Univariate and multivariate regression analyses were used to identify possible predictors for the CSI score in 2890 patients with chronic pain. The CSI score is associated with all independent factors and has a low association with pain severity in women and a low association with pain severity, age, and body mass index in men. The newly established CSI cutoff values are lower than in previous studies and different per sex, which might be of clinical relevance in daily practice and importance in research.