Pharmacological Treatment of Musculoskeletal Pain

Musculoskeletal pain management should accommodate patientchoice, sensory and emotional aspects of pain, its diverse mechanismsin both peripheral and central nervous systems, and its context,including diagnosis, disability and co-morbidities, emotions, andpast experiences. Musculoskeletal disorders may broadly be classified as inflammatory (characterised by specific immune responses, as in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis), or non-inflammatory (e.g. osteoarthritis, neck or low back pain). Mechanisms also differ between acute and chronic pain. People with chronic musculoskeletal conditions often continue to experience acute pain. Acute pain on a background of chronic musculoskeletal disease may respond differently to treatment than in a healthy, usually pain-free individual. All patients should consider tailored pharmacological and non-pharmacological management strategies that can help pain irrespective of diagnosis, alongside diagnosis-specific medications

Αποκρυφιστικές ερμηνείες του Ησυχασμού

Saint Grégoire, Archevêque de Thessalonique, Palamas, appartient aux personnalités des pères suprêmes de l'Église Orthodoxe. Sa personne compte parmi les combattants suprêmes et représentants de la Foi Orthodoxe, aux maîtres errants de la vraie Théologie.Les catholiques et les protestants ont adopté le terme inadmissible «Palamismos» afin de présneter l' instruction de Saint Grégoire comme soidisant une instruction personnelle et de caractére particulier sans reroncer à leur polémique et critique contre le saint père.Mais à propos de la personne de Saint Grégoire de Palamas et la méthode d' hésychasme aux années plus récentes, on a aussi essayé de différentes tentatives de leur approche occultive, leur représentation et interprétation.a) Toute l'argumentation des efforts occultifs essaie de présenter l'Hésychasme dans le cadre ésotérisme comme un enseignement et une technique secrets, confidentiels qui s'adressent à un certain cercle étroit des initiés.b) L'instruction de Saint Grégoire Palamas est littéralement violée comme ils essaient de présenter ses positions théologiques et donner un sens avec un contenu qu' on rencontre à des textes et espaces occultifs.c) L'instruction de Saint Grégoire Palamas est présentée tantôt comme une forme d' instruction et de technique de caractère ésotérisme et tantôt ils essaient de les niveler avec des pratiques de religions en dehors du christianisme(Hindouisme - Bouddhisme, Soufisme).d) L'instruction de Saint Grégoire Palamas est entièrement présentée avec de déformations et en dehors de toute base historique, ecclésiastique et théologique. Ce qu'on mentionne comme positions du saint est tout à fait contraire à ce qu'en réalité le saint père enseigne. Pour ceux-ci, il est considéré comme un encore représentant du mysticisme à une base proprement occultive- intérieure, lequel exprime ses expériences personnelles de type ésotérique.e) Toute la tradition d' hésychasme et différents textes de la Philocalie constituent, dans le cadre de l' interprétation occultive de l'Hésychasme une forme parmi plusieurs, de l' expression de l' espace-temps et de l' évolution d' ésotérisme. Dans le même cadre, on fait une mention d' extrait et usage des pères et textes plus vieux et plus récents, non pas correctement compris, en dehors de leur connexité de sens plus large et certainement en dehors de leur sens ecclésiastique et théologique.Saint Grégoire, Archevêque de Thessalonique, Palamas, appartient aux personnalités des pères suprêmes de l'Église Orthodoxe. Sa personne compte parmi les combattants suprêmes et représentants de la Foi Orthodoxe, aux maîtres errants de la vraie Théologie.Les catholiques et les protestants ont adopté le terme inadmissible «Palamismos» afin de présneter l' instruction de Saint Grégoire comme soidisant une instruction personnelle et de caractére particulier sans reroncer à leur polémique et critique contre le saint père.Mais à propos de la personne de Saint Grégoire de Palamas et la méthode d' hésychasme aux années plus récentes, on a aussi essayé de différentes tentatives de leur approche occultive, leur représentation et interprétation.a) Toute l'argumentation des efforts occultifs essaie de présenter l'Hésychasme dans le cadre ésotérisme comme un enseignement et une technique secrets, confidentiels qui s'adressent à un certain cercle étroit des initiés.b) L'instruction de Saint Grégoire Palamas est littéralement violée comme ils essaient de présenter ses positions théologiques et donner un sens avec un contenu qu' on rencontre à des textes et espaces occultifs.c) L'instruction de Saint Grégoire Palamas est présentée tantôt comme une forme d' instruction et de technique de caractère ésotérisme et tantôt ils essaient de les niveler avec des pratiques de religions en dehors du christianisme(Hindouisme - Bouddhisme, Soufisme).d) L'instruction de Saint Grégoire Palamas est entièrement présentée avec de déformations et en dehors de toute base historique, ecclésiastique et théologique. Ce qu'on mentionne comme positions du saint est tout à fait contraire à ce qu'en réalité le saint père enseigne. Pour ceux-ci, il est considéré comme un encore représentant du mysticisme à une base proprement occultive- intérieure, lequel exprime ses expériences personnelles de type ésotérique.e) Toute la tradition d' hésychasme et différents textes de la Philocalie constituent, dans le cadre de l' interprétation occultive de l'Hésychasme une forme parmi plusieurs, de l' expression de l' espace-temps et de l' évolution d' ésotérisme. Dans le même cadre, on fait une mention d' extrait et usage des pères et textes plus vieux et plus récents, non pas correctement compris, en dehors de leur connexité de sens plus large et certainement en dehors de leur sens ecclésiastique et théologique

Central sensitisation as a predictor of self-management in chronic low back pain

Background: Chronic low back pain (CLBP) is one of the most prevalent reasons people seek healthcare assistance worldwide. Guidelines for managing CLBP prioritise the development of self-management strategies. Levels of central sensitisation (CS) may contribute to the relatively poor efficacy of treatments aiming to facilitate self-management. CS might be a dominant factor predicting worse self-management in people with CLBP following interventions aiming to improve such outcomes. Quantitative sensory testing (QST) may provide reliable and valid indices of CS and it may predict musculoskeletal pain and disability. CS might be associated with increasing psychological distress, pain, fatigue and catastrophisation which might also be predictors of ineffective self-management. CS has also been associated in people with knee pain with self-report measures of widespread pain distribution (reported by shading a pain manikin) or a self-report Central Mechanisms Trait score, comprising of items addressing depression, anxiety, neuropathic-like symptoms, pain distribution, catastrophising, sleep, fatigue and cognitive difficulties. Objectives: [1] to systematically review the literature in order to determine the ability of QST to predict musculoskeletal outcomes; [2] to establish the reliability and validity of distinct QST modalities as classification and measurement tools of CS; [3] to establish a cut off for number of body sites shaded on a self-reported pain manikin that best identifies those with widespread pain and explore whether certain self-reported items taken to indicate central mechanisms involvement contribute to a single latent trait in individuals with CLBP; [4] to determine whether different CS indices are associated specifically with self-management/self-care outcomes at a single time-point; [5] to test whether any cross-sectional associations between baseline CS indices and self-management/self-care outcomes are also present longitudinally, after participants have undertaken an intervention programme that aimed to improve such outcomes. Methods: A systematic literature review (SLR) was conducted to collate the evidence regarding the ability of QST to predict pain, disability and negative affect using searches of 6 databases up to April 2018. Title screening, data extraction, and methodological quality assessments were performed independently by 2 reviewers. Associations were reported between baseline QST and outcomes using adjusted (β) and unadjusted (r) correlations. Reliability of Pressure Pain Detection Threshold (PPT), Temporal Summation (TS) and Conditioned Pain Modulation (CPM) conducted at a site distant from the low back were assessed in healthy participants (n=25) and individuals with CLBP (n=25). The QST test site was the dominant forearm and conditioning site the contralateral arm. Pain distribution was classified according to criteria proposed by the American College of Rheumatology (ACR) and other research groups. Receiver operating characteristics (ROC) analysis established the cut-off point for the optimal number of painful sites needed to classify low PPT (1st quartile). Confirmatory factor analysis (CFA) was used to assess model fit and produce a single Central Mechanisms Trait score based on unique items form 8 distinct self-reported tools. The ability of baseline indices of CS (PPT, TS, CPM, number of painful sites on a manikin, and Central Mechanisms Trait score) to predict self-management outcomes at 3-months follow-up was assessed in individuals with CLBP (n=97) participating in a cognitive behavioural therapy (CBT)-based group physiotherapy intervention, which aimed to facilitate self-management. Self-management was measured in 8 discrete domains; health-directed behaviour, positive engagement in life, self-monitoring and insight, constructive attitudes and approaches, skill and technique acquisition, social integration and support, health services navigation and emotional distress. Pain (numerical rating scale), depression/anxiety (hospital anxiety-depression scale), fatigue (fatigue severity scale) and catastrophising (pain catastrophising scale) were also measured. Results: The SLR identified 37 eligible studies (n=3860 participants). Meta-analysis revealed that baseline QST predicted musculoskeletal pain (mean r=0.31, 95%CI: 0.23 to 0.38, n=1057 participants) and disability (mean r=0.30, 95%CI: 0.19 to 0.40, n=290 participants). Baseline modalities quantifying central mechanisms such as TS and CPM were associated with follow-up pain (TS: mean r=0.37, 95%CI: 0.17 to 0.54; CPM: r=0.36, 95%CI: 0.20 to 0.50), and baseline mechanical threshold modalities were predictive of follow-up disability (mean r=0.25, 95%CI: 0.03 to 0.45). Test-retest and inter-rater reliability were high for PPT and TS in both normal and CLBP populations (ICC=0.76 to 0.92) but low for CPM (ICC=0.43 and 0.46 respectively). In people with CLBP (n=97), ROC analysis determined that >9/24 painful sites optimally predicted low PPT at the forearm (AUC=0.67, 95%CI: 0.55 to 0.80). The single-factor Central Mechanisms Trait model showed a good fit to the data (CFI=0.92, TLI=0.88; RMSEA=0.09; SRMR=0.07; x2(df)=34.19(20)). Follow-up questionnaires were completed by 87 people with CLBP (67% female, mean age 65y). Low PPT, inefficient CPM, the ACR and >9/24 classification criteria and the Central Mechanisms trait predicted less positive engagement in life (r=-0.54 to 0.31, p<0.05), low PPT and inefficient CPM each predicted increased emotional distress (PPT: r=-0.21, p<0.05; CPM: r=-0.29, p=0.01), and low PPT predicted worse social integration and support (r=0.28, p<0.01) at 3 months. Baseline Central Mechanisms trait scores predicted worse performance in health directed behaviour, positive engagement in life, constructive attitudes and approaches, social integration and support and emotional distress at 3-months (r=-0.56 to 0.54, p<0.05). In multivariate regression models exploring the relationship between baseline CS indices (QST modalities, widespread pain identification methods, Central Mechanisms trait) and self-management outcomes, adjusted for other variables (age, sex, depression, catastrophisation, pain and fatigue), low PPT, inefficient CPM and Central Mechanisms trait scores, remained significantly associated (p<0.05) with social integration and support, positive engagement in life and constructive attitudes and approaches at 3 months respectively. Conclusion: QST can predict musculoskeletal outcomes across a range of musculoskeletal conditions and discrete pain hypersensitivity indices (PPT and TS) demonstrate high reliability as pain quantification tool. Baseline indices of high CS can predict reduced ability of individuals with CLBP to self-manage their condition 3 months after commencing a CBT-based group physiotherapy intervention. Self-management is a multidimensional concept and its influence by factors other than CS merits further research. Treatments which specifically target CS might help remove barriers to self-management in people with CLBP

Investigating the Potential of the Inter-IXP Multigraph for the Provisioning of Guaranteed End-to-End Services

In this work, we propose utilizing the rich connectivity between IXPs and ISPs for inter-domain path stitching, supervised by centralized QoS brokers. In this context, we highlight a novel abstraction of the Internet topology, i.e., the inter-IXP multigraph composed of IXPs and paths crossing the domains of their shared member ISPs. This can potentially serve as a dense Internet-wide substrate for provisioning guaranteed end-to-end (e2e) services with high path diversity and global IPv4 address space reach. We thus map the IXP multigraph, evaluate its potential, and introduce a rich algorithmic framework for path stitching on such graph structures.Comment: Proceedings of ACM SIGMETRICS '15, pages 429-430, 1/1/2015. arXiv admin note: text overlap with arXiv:1611.0264

Do maladaptive beliefs delay whiplash associated disorders (WAD): A systematic review

The purpose of the study is to try to establish if maladaptive beliefs effect recovery times and poor outcomes in whiplash associated disorders (WAD). In May 2017 the following databases were searched from their inception until June 2017: SPORT Discuss, CINAHL, PsycINFO, MEDLINE, Ovid MEDLINE, Cochrane, AMED, Embase. A combination of sensitive search strategies was used for locating articles on maladaptive beliefs and WAD. Hand-searching of relevant journals and citation tracking were used to maximise the identified study pool. A total of 189 references were retrieved and an additional three studies were identified through different sources, 178 remained after the removal of duplicates. For 43 references, the full text was assessed, and 7 studies were included. The methodological quality was assessed independently by two assessors. Data extraction was carried out using a standardised data extraction form. Most articles scored a high overall quality and fourteen percent (14%) of articles (1 out of 7) were rated with moderate overall quality. Meta-analysis was not undertaken due to the heterogeneity of prognostic factors, outcome measures and methods used. Four out of the seven studies presented a correlation between catastrophising and disability in at least one follow-up time point (3, 6 or 12 months) whilst three studies found a correlation between fear-avoidance and disability. Four of the studies showed an association between maladaptive beliefs (catastrophising or fear avoidance) and pain and two found a negative effect. Our findings show that outcomes, such as pain and disability, were found to be associated with maladaptive beliefs (catastrophising and fear avoidance)

Validation of a questionnaire for central nervous system aspects of joint pain: the CAP questionnaire

BackgroundNeuropathic-like pain, fatigue, cognitive difficulty, catastrophizing, anxiety, sleep disturbance, depression and widespread pain associate with a single factor in people with knee pain. We report the Central Aspects of Pain questionnaire (CAP) to characterize this across painful musculoskeletal conditions.MethodsCAP was derived from the 8-item CAP-Knee questionnaire, and completed by participants with joint pain in the Investigating Musculoskeletal Health and Wellbeing survey. Subgroups had OA, back pain or FM. Acceptability was evaluated by feedback and data missingness. Correlation coefficients informed widespread pain scoring threshold in relation to the other items, and evaluated associations with pain. Factor analysis assessed CAP structure. Intraclass Correlation Coefficient (ICC) between paper and electronic administration assessed reliability. Friedman test assessed score stability over 4 years in people reporting knee OA.ResultsData were from 3579 participants (58% female, median age 71 years), including subgroups with OA (n = 1158), back pain (n = 1292) or FM (n = 177). Across the three subgroups, ≥10/26 painful sites on the manikin scored widespread pain. Reliability was high [ICC = 0.89 (95% CI 0.84–0.92)] and CAP scores fit to one- and two-factor model, with a total CAP score that was associated with pain severity and quality (r = 0.50–0.72). In people with knee pain, CAP scores were stable over 4 years at the group level, but displayed significant temporal heterogeneity within individual participants.ConclusionsCentral aspects of pain are reliably measured by the CAP questionnaire across a range of painful musculoskeletal conditions, and is a changeable state

Quantitative sensory testing and predicting outcomes for musculoskeletal pain, disability, and negative affect: a systematic review and meta-analysis

Hypersensitivity due to central pain mechanisms can influence recovery and lead to worse clinical outcomes, but the ability of quantitative sensory testing (QST), an index of sensitisation, to predict outcomes in chronic musculoskeletal disorders remains unclear. We systematically reviewed the evidence for ability of QST to predict pain, disability and negative affect using searches of CENTRAL, MEDLINE, EMBASE, AMED, CINAHL and PubMed databases up to April 2018. Title screening, data extraction, and methodological quality assessments were performed independently by 2 reviewers. Associations were reported between baseline QST and outcomes using adjusted (β) and unadjusted (r) correlations. Of the 37 eligible studies (n=3860 participants), 32 were prospective cohort studies and 5 randomised controlled trials. Pain was an outcome in 30 studies, disability in 11 and negative affect in 3. Metaanalysis revealed that baseline QST predicted musculoskeletal pain (mean r=0.31, 95%CI: 0.23 to 0.38, n=1057 participants) and disability (mean r=0.30, 95%CI: 0.19 to 0.40, n=290 participants). Baseline modalities quantifying central mechanisms such as temporal summation (TS) and conditioned pain modulation (CPM) were associated with follow-up pain (TS: mean r=0.37, 95%CI: 0.17 to 0.54; CPM: r=0.36, 95%CI: 0.20 to 0.50), whereas baseline mechanical threshold modalities were predictive of followup disability (mean r=0.25, 95%CI: 0.03 to 0.45). QST indices of pain hypersensitivity might help develop targeted interventions aiming to improve outcomes across a range of musculoskeletal conditions

An observational study of centrally facilitated pain in individuals with chronic low back pain

Central pain facilitation can hinder recovery in people with chronic low back pain (CLBP). The aim of this observational study was to investigate whether indices of centrally facilitated pain are associated with pain outcomes in a hospital-based cohort of individuals with CLBP undertaking a pain management programme. Participants provided self-report and pain sensitivity data at baseline (n=97), and again 3-months (n=87) after a cognitive behavioural therapy-based group intervention including physiotherapy. Indices of centrally facilitated pain were; Pressure Pain detection Threshold (PPT), Temporal Summation (TS) and Conditioned Pain Modulation (CPM) at the forearm, Widespread Pain Index (WPI) classified using a body manikin, and a Central Mechanisms Trait (CMT) factor derived from 8 self-reported characteristics of anxiety, depression, neuropathic pain, fatigue, cognitive dysfunction, pain distribution, catastrophizing and sleep. Pain severity was a composite factor derived from Numerical Rating Scales. Cross-sectional and longitudinal regression models were adjusted for age and sex. Baseline CMT and WPI each was associated with higher pain severity (CMT: r=0.50, p<0.001, WPI: r=0.21, p=0.04) at baseline as well as at 3 months (CMT: r=0.38, p<0.001, WPI: r=0.24, p=0.02). High baseline CMT remained significantly associated with pain at 3 months after additional adjustment for baseline pain (β=2.45, p=0.04, R2=0.25, p<0.0001). QST indices of pain hypersensitivity were not significantly associated with pain outcomes at baseline or at 3 months. In conclusion, central mechanisms beyond those captured by QST are associated with poor CLBP outcome and might be targets for improved therapy

Mechanisms of manipulation:a systematic review of the literature on immediate anatomical structural or positional changes in response to manually delivered high-velocity, low-amplitude spinal manipulation

Background: Spinal manipulation (SM) has been claimed to change anatomy, either in structure or position, and that these changes may be the cause of clinical improvements. The aim of this systematic review was to evaluate and synthesise the peer-reviewed literature on the current evidence of anatomical changes in response to SM. Methods: The review was registered with PROSPERO (CRD42022304971) and reporting was guided by the standards of the PRISMA Statement. We searched Medline, Embase, CINAHL, AMED, Cochrane Library all databases, PEDro, and the Index to Chiropractic Literature from inception to 11 March 2022 and updated on 06 June 2023. Search terms included manipulation, adjustment, chiropractic, osteopathy, spine and spine-related structures. We included primary research studies that compared outcomes with and without SM regardless of study design. Manipulation was defined as high-velocity, low-amplitude thrust delivered by hand to the spine or directly related joints. Included studies objectively measured a potential change in an anatomical structure or in position. We developed a novel list of methodological quality items in addition to a short, customized list of risk of bias (RoB) items. We used quality and RoB items together to determine whether an article was credible or not credible. We sought differences in outcomes between SM and control groups for randomised controlled trials and crossover studies, and between pre- and post-SM outcomes for other study designs. We reported, in narrative form, whether there was a change or not. Results: The search retrieved 19,572 articles and 20 of those were included for review. Study topics included vertebral position (n = 3) facet joint space (n = 5), spinal stiffness (n = 3), resting muscle thickness (n = 6), intervertebral disc pressure (n = 1), myofascial hysteresis (n = 1), and further damage to already damaged arteries (n = 1). Eight articles were considered credible. The credible articles indicated that lumbar facet joint space increased and spinal stiffness decreased but that the resting muscle thickness did not change. Conclusion: We found few studies on this topic. However, there are two promising areas for future study: facet joint space and spinal stiffness. A research strategy should be developed with funding for high quality research centres

The interrater and test–retest reliability of 3 modalities of quantitative sensory testing in healthy adults and people with chronic low back pain or rheumatoid arthritis

Introduction: Quantitative Sensory Testing (QST) modalities used to assess central pain mechanisms require different protocols in people with different musculoskeletal conditions.Objectives: We aimed to explore the possible effects of musculoskeletal diagnosis and test site on QST interrater and test–retest reliability.Methods: The study included participants with rheumatoid arthritis (RA, n = 18; QST conducted on lower leg) and low back pain (LBP, n = 25; QST conducted on forearm), plus 45 healthy control participants (n = 20 QST on lower leg and n = 25 QST on forearm). Test–retest reliability was assessed from QST conducted 1 to 3 weeks apart. Quantitative sensory testing modalities used were pressure pain detection threshold (PPT) at a site distant to tissue pathology, temporal summation (TS), and conditioned pain modulation (CPM). Temporal summation was calculated as difference or ratio of single and repeated punctate stimuli and unconditioned thresholds for CPM used single or mean of multiple PPTs. Intraclass correlation coefficients (ICCs) were compared between different subgroups.Results: High to very high reliability was found for all assessments of PPT and TS across anatomical sites (lower leg and forearm) and participants (healthy, RA, and LBP) (ICC ≥ 0.77 for PPT and ICC ≥ 0.76 for TS). Reliability was higher when TS was calculated as a difference rather than a ratio. Conditioned pain modulation showed no to moderate reliability (ICC = 0.01–0.64) that was similar between leg or forearm, and between healthy people and those with RA or LBP.Conclusion: PPT and TS are transferable tools to quantify pain sensitivity at different testing sites in different musculoskeletal diagnoses. Low apparent reliability of CPM protocols might indicate minute-to-minute dynamic pain modulation