The Musculoskeletal Wrangler

The Musculoskeletal Wrangler I am an APA Musculoskeletal Physiotherapist and an emerging APA "Pain" Physio passionate about evidence based practice (EBP).

This page keeps me accountable with EBP, and can hopefully serve as a useful resource for health professionals and consumers.

Placebo:Part 4: insights for clinical trials and clinical practiceBACKGROUND:🔎Placebo and nocebo effects are psychobiolo...
08/04/2026

Placebo:
Part 4: insights for clinical trials and clinical practice
BACKGROUND:
🔎Placebo and nocebo effects are psychobiological responses triggered by the context of treatment rather than the treatment itself. Increasing recognition that these effects are driven by mechanisms such as expectations, learning, and contextual cues.
DEFINITIONS:
📝Placebo and nocebo are defined as positive and negative health outcomes resulting from expectations, context, and meaning attributed to treatment, respectively.
📍A recent scoping review by Bagnis et al. (2025) mapped existing evidence on placebo and nocebo responses and their mechanisms, to identify implications for trials and healthcare.
CLINICAL TRIALS
👨‍🔬Clinical trials must be controlled and measured to ensure validity.
📈Placebo and nocebo effects can inflate or obscure true treatment effects, and increase variability in outcomes. Nocebo may lead to high drop outs or misattribution of adverse events
📝Recommendations: careful trial design with standardisation of participant information and measurement of expectations and contextual factors.
CLINICAL PRACTICE
👩‍⚕️Clinical practice must be leveraged to improve outcomes and minimised to reduce harm through effective communication and therapeutic context.
📈Clinicians can ethically harness placebo effects through positive but realistic framing of treatment benefits, while building a strong therapeutic alliance.
📉Strategies to minimise nocebo effects include balanced risk-benefit analysis, and the use of reassuring, non-alarmist language.
SUMMARY:
📖Placebo and nocebo effects are powerful, measurable, and clinically relevant phenomena. They arise from expectations, learning, and contextual cues, with identifiable neurobiological pathways.
📚In clinical trials, they must be controlled and measured to ensure validity. Whereas, in clinical practice, they can be leveraged to improve outcomes and minimised to reduce harm through effective communication and therapeutic context.
MW
Reference:
Bagnis A, Meeuwis SH, Haas JW, O’Keeffe M, Bajcar EA, Babel P, Evers AWM, Glogan E, … and on behalf of the PANACEA Consortium. A scoping review of placebo and nocebo responses and effects: insights for clinical trials and practice. Health Psychology Review,2025;19(2):409-447.

PlaceboPart 3: mechanismsBACKGROUND:🔎Placebo effects arise not from the treatment itself, but from the context surroundi...
08/04/2026

Placebo
Part 3: mechanisms
BACKGROUND:
🔎Placebo effects arise not from the treatment itself, but from the context surrounding treatment. These effects can produce real changes in symptoms (especially pain), mediated by genuine psychobiological phenomena with measurable neurophysiological mechanisms.
📍An important narrative review by Price et al. (2008) synthesised the existing evidence and advances conceptual understanding of the placebo effect, rather than a systematic or scoping review.
MECHANISMS (see image):
🧠Neuroimaging and pharmacological studies show activation of endogenous opioid systems and dopaminergic reward pathways. Placebo responses are therefore biologically grounded, not merely subjective or imagined
SUMMARY:
📖Placebo effects arise through the interaction of expectation and learned associations, which activate brain systems involved in pain modulation, reward, and emotion. These processes engage endogenous opioids, dopaminergic pathways, and broader brain networks to produce real, measurable changes in symptom perception and experience.
MW
Reference:
Price DD, Finniss DG, Benedetti F. A comprehensive review of the placebo effect: recent advances and current thought. Annu Rev Psychol. 2008;59:565–590.

PlaceboPart 2: contextual factorsBACKGROUND:🔎Placebo effects arise not from the treatment itself, but from the context s...
08/04/2026

Placebo
Part 2: contextual factors
BACKGROUND:
🔎Placebo effects arise not from the treatment itself, but from the context surrounding treatment. These effects can produce real changes in symptoms (especially pain), mediated by genuine psychobiological phenomena with measurable neurophysiological mechanisms.
📍An important narrative review by Price et al. (2008) synthesised the existing evidence and advances conceptual understanding of the placebo effect, rather than a systematic or scoping review.
CONTEXTUAL FACTORS (see image):
SUMMARY:
📖Placebo effects are complex, brain-mediated responses shaped by context, expectation, and learning. Rather than being incidental or deceptive, placebo effects are integral to therapeutic outcomes and should be consciously integrated into both clinical care and research design.
MW
Reference:
Price DD, Finniss DG, Benedetti F. A comprehensive review of the placebo effect: recent advances and current thought. Annu Rev Psychol. 2008;59:565–590.

Placebo:Part 1: de-stigmatiseBACKGROUND:🔎Contrary to popular belief, placebo effects are actually real, measurable, and ...
08/04/2026

Placebo:
Part 1: de-stigmatise
BACKGROUND:
🔎Contrary to popular belief, placebo effects are actually real, measurable, and clinically meaningful.
📍An influential perspective review by Arnold et al. (2015) synthesised contemporary evidence to challenge the prevailing misconception that placebo effects are inherently fake, deceptive, or clinically irrelevant. The authors argue that placebo effects are not simply linked to inert treatments, but instead emerge from the broader context of care, including clinician–patient interactions, expectations, and the meaning attributed to treatment.
MECHANISMS:
Placebo effects are driven by several interacting factors that can modulate pain and symptom perception:
🧠Expectations: the belief that a treatment will help can directly influence outcomes
💪Conditioning: prior experiences can reinforce responses
🗣️Clinician-patient interaction: therapeutic alliance can enhance treatment effects
Context and meaning including rituals of care can shape responses
ETHICAL CONSIDERATIONS:
👨‍🔬Traditional concerns are that placebo interventions involve deception, potentially undermining trust. Contemporary research however, demonstrates that placebo effects can occur without deception (e.g., open-label placebo) and that ethical care should focus on transparency and patient benefit
CLINICAL IMPLICATIONS:
👩‍⚕️Placebo effects are already embedded in routine care via communication and therapeutic relationships. Clinicians should therefore harness these effects by using positive, realistic framing of treatment expectations, while also fostering a strong therapeutic alliance.
SUMMARY:
📖Placebo effects are valid psychobiological responses, not merely artefacts or deception. Good clinical care should integrate an understanding of context, communication, and expectation as active ingredients in healing.
MW
Reference:
Arnold M, Kerridge I, Finniss D. Destigmatizing the placebo effect, peer commentary, American Journal of Bioethics, 2015, 15(10) pp. 21 - 23

Conditioned pain modulation (CPM):Part 12: lifestyle factors (physical activity)BACKGROUND:🔎Lifestyle factors such as ph...
03/04/2026

Conditioned pain modulation (CPM):
Part 12: lifestyle factors (physical activity)
BACKGROUND:
🔎Lifestyle factors such as physical activity may partly explain this variability, but evidence has been limited and inconclusive.
📍A cross-sectional study by Van Oosterwijck et al. (2024) examined whether habitual physical activity predicted CPM magnitude in 105 healthy adults. The authors used a 7-day monitoring program using a self-reported questionnaire and an objective accelerometry instrument.
FINDINGS:
🗣️Self-reported physical activity predicted 7% of CPM magnitude
🟢Walking predicted 4.8% of variation in CPM effect
🟢Moderate intensity physical activity predicted 10.2%
🔴Accelerometery did not predict CPM
Male s*x and older age also predicted greater CPM effects
IMPLICATIONS:
📖Regular physical activity, especially walking and moderate intensity activity, is associated with greater endogenous pain inhibitory capacity in healthy adults and may act as a modifiable predictor of CPM
📚Objective measurement differences (self report vs. accelerometry) suggest how physical activity is measured matters for interpreting its relationship with pain modulation.
MW
Reference:
Van Oosterwijck S, Meeus M, van Der Wekken J, Dhondt E, Billens A, Van Oosterwijck J. Physical activity is predictive of conditioned pain modulation in healthy individuals: a cross-sectional study. J Pain. 2024 Nov;25(11):104639. doi:10.1016/j.jpain.2024.104639

Conditioned pain modulation (CPM):Part 11: predictorsBACKGROUND:🔎Identifying predictors of this dysfunction could help p...
03/04/2026

Conditioned pain modulation (CPM):
Part 11: predictors
BACKGROUND:
🔎Identifying predictors of this dysfunction could help prevent chronicity and guide early interventions. Existing literature has demonstrated mixed results, and no consensus existed on which factors reliably predict altered pain modulation.
📍A systematic review by Clark et al. (2017) aimed to identify factors that predict altered central pain modulation (a key mechanism involving dysregulated central nervous system processing) in people with chronic musculoskeletal pain. The authors evaluated 9 studies where baseline measurements were taken during pre morbid or acute stages, and outcomes were assessed at least three months later.
FINDINGS:
Moderate evidence supported two primary predictors of altered CPM:
🟢High sensory sensitivity via QST
🟢Psychological factors such as somatisation and negative recovery expectations
🔴Poor predictors included pain intensity, duration and disability
IMPLICATIONS:
🔆Early identification of high-risk individuals based on sensory and psychological factors may guide targeted interventions to prevent chronic pain development
🔆CPM is multifactorial, reflecting the interaction of sensory processing and psychological components
SUMMARY:
📖High sensory sensitivity and psychological distress (somatisation, poor recovery expectations) are the strongest predictors of altered central pain modulation in chronic musculoskeletal pain populations.
📚These findings emphasise a multidimensional approach to understanding and managing central pain processing, with potential for early risk stratification and intervention.
MW
Reference:
Clark J, Yeowell G, Nijs J, Goodwin PC. What are the predictors of altered central pain modulation in chronic musculoskeletal pain populations? A systematic review. Pain Physician. 2017;20(6):487–500.

Conditioned pain modulation (CPM):Part 10: emotional stateBACKGROUND:🔎Psychological factors, particularly negative emoti...
02/04/2026

Conditioned pain modulation (CPM):
Part 10: emotional state
BACKGROUND:
🔎Psychological factors, particularly negative emotional states such as anxiety, stress, and depression, are thought to influence pain processing, but their effect on CPM has been unclear and inconsistently reported.
📍A narrative review by Horn-Hofmann & Lautenbacher (2019) examining experimental and clinical studies investigating whether negative emotional states alter CPM responses. The paper synthesises evidence from studies manipulating mood (e.g., induced stress or anxiety) and those assessing naturally occurring affective states.
FINDINGS:
🟠Evidence is mixed and inconsistent.
🟢Some studies show reduced CPM efficiency under negative emotional states (suggesting impaired endogenous inhibition).
🔴Others reported no effect or even enhanced CPM, depending on methodology and variability related to type and intensity of emotion, experimental paradigms and individual differences.
IMPLICATIONS:
📚Clinical interpretation of CPM (e.g., as a biomarker in chronic pain) should consider emotional and contextual factors.
SUMMARY:
📖Negative emotional states can influence conditioned pain modulation, but the direction and magnitude of this effect are inconsistent. CPM should be viewed as a dynamic measure shaped by both neurophysiological and psychological processes rather than a fixed indicator of pain inhibitory capacity.
MW
Reference:
Horn-Hofmann C, Lautenbacher S. Is conditioned pain modulation (CPM) affected by negative emotional state? Pain. 2019;160(11):2416–2425.

Conditioned pain modulation (CPM):Part 9: expectations and attentionBACKGROUND:🔎Growing evidence suggests that cognitive...
31/03/2026

Conditioned pain modulation (CPM):
Part 9: expectations and attention
BACKGROUND:
🔎Growing evidence suggests that cognitive factors such as expectations and attention, may influence CPM responses. This challenges the assumption that CPM purely reflects physiological pain inhibitory capacity.
📍A recent meta-analysis by Billens et al. (2024) synthesized the data of 21 experimental studies (n=1300) examining the effects of expectations and attention on CPM outcomes.
EXPECTATIONS have a significant influence on CPM (moderate effect size):
📈Positive expectations (e.g., believing pain will decrease) enhances CPM effect ~ placebo
📉Negative expectations (e.g., believing pain will not decrease) reduces or abolishes CPM effect ~ nocebo
ATTENTION has a less consistent influence on CPM (small/variable effect size):
📈Distraction can enhance CPM, thereby reducing pain intensity
📉Focusing on pain may reduce CPM effectiveness, thereby amplifying pain intensity
PROPOSED MECHANISMS:
🔆Expectations influence CPM through predictive, placebo/nocebo, and descending inhibitory mechanisms, while attention alters CPM by modulating cognitive resources and pain salience. Together, they demonstrate that CPM is not purely physiological, but strongly shaped by top-down cognitive processes.
IMPLICATIONS:
📖Expectations significantly influence CPM, while attention plays a smaller, less consistent role. These findings highlight that CPM reflects a combination of cognitive and physiological processes, rather than a purely objective measure of pain inhibition. CPM is therefore not purely a physiological measure, as it is influenced by cognitive context
MW
Reference:
Billens A, Van Oosterwijck S, Dhondt E, Meeus M, De Greef I, Van Damme S, Van Oosterwijck J. The influence of expectations and attention on conditioned pain modulation: a systematic review and meta-analysis. Clinical Psychology Review. 2024;114:102517.

Conditioned pain modulation (CPM):Part 8: personal factorsBACKGROUND:🔎The influence of individual (personal) factors on ...
31/03/2026

Conditioned pain modulation (CPM):
Part 8: personal factors
BACKGROUND:
🔎The influence of individual (personal) factors on CPM responses in healthy individuals is not fully understood. Identifying these factors is important for interpreting CPM results and for its potential use as a clinical biomarker.
📍A systematic review by Hermans et al. (2016) examined how personal factors influence CPM in healthy populations. The authors synthesized findings across 32 experimental studies (n=1500) that assessed CPM using various paradigms (e.g., pressure, thermal, cold pressor stimuli).
DEMOGRAPHIC:
🟢Males consistently demonstrated greater CPM effects than females
🟠Increasing age was inconsistently associated with reduced CPM
PYSCHOLOGICAL FACTORS:
🟢Expectations and attention can modulate CPM responses
🟠Higher levels of pain catastrophizing were often linked to reduced CPM efficiency
🟠Anxiety and depression demonstrated inconsistent associations
LIFESTYLE & BEHAVIOURAL:
🟢Physical activity demonstrated enhanced CPM
🟢Poor sleep was associated with impaired pain inhibition
🟠Substance use (eg: caffeine & ni****ne) demonstrated variable and inconclusive findings
PHYSIOLOGICAL & BIOLOGICAL:
🟠Hormonal influences (eg: menstrual cycle) demonstrated inconsistent findings
🟠Genetic factors may have a potential role, more evidence is required.
IMPLICATIONS:
🔆CPM is not a static, isolated measure, it is influenced by multiple interacting personal factors.
🔆Variability in CPM across individuals may reflect normal biological and psychological differences, not just pathology
🔆Using CPM as a biomarker for chronic pain, as results may be confounded by non-pathological influences
MW
Reference:
Hermans L, Van Oosterwijck J, Goubert D, Goudman L, Crombez G, Calders P, Meeus M. Inventory of personal factors influencing conditioned pain modulation in healthy people: a systematic literature review. Pain Practice. 2016;16(6):758-769.

Conditioned pain modulation (CPM):Part 7: reliabilityBACKGROUND:🔎CPM is increasingly used to investigate pain processing...
31/03/2026

Conditioned pain modulation (CPM):
Part 7: reliability
BACKGROUND:
🔎CPM is increasingly used to investigate pain processing in both healthy individuals and chronic pain patients. However, its reliability across studies and populations remains unclear, limiting its clinical and research utility.
📍A recent meta-analysis by Nuwailati et al. (2023) synthesized the evidence from 25 studies involving healthy participants and chronic pain patients to assess intra- and inter-session reliability, including factors that may influence variability such as stimulus type, location, and protocol differences.
RELIABILITY:
📈CPM generally showed moderate to good intra-rater reliability in healthy participants, meaning that repeated measurements by the same examiner were reasonably consistent.
👩‍⚕️Results however, were influenced by testing protocols, pain modality (pressure, thermal, or electrical), and conditioning stimuli.
📉In chronic pain patients, intra-rater reliability was more variable, likely reflecting fluctuations in endogenous pain modulation and symptom variability.
📚Fewer studies assessed inter-rater reliability, but available evidence suggests lower reliability compared with intra-rater measures.
CONSIDERATIONS:
📚Reliability was higher in studies using standardized and reproducible protocols, particularly with consistent conditioning stimuli and test sites.
SUMMARY:
📖Understanding CPM reliability is critical for its use as a potential biomarker in chronic pain research and for guiding personalized pain management strategies. For CPM to be a useful biomarker in research or clinical settings, consistent protocols and training of raters are essential.
💡Variability in chronic pain populations underscores the need to interpret CPM results cautiously and potentially repeat measurements to improve confidence.
MW
Reference:
Nuwailati R, Bobos P, Drangsholt M, Curatolo M. Reliability of conditioned pain modulation in healthy individuals and chronic pain patients: a systematic review and meta-analysis. Pain. 2023;164(5):987–1001.

Conditioned pain modulation (CPM):Part 6: validity as a biomarkerBACKGROUND:🔎CPM is widely used as an indicator of desce...
31/03/2026

Conditioned pain modulation (CPM):
Part 6: validity as a biomarker
BACKGROUND:
🔎CPM is widely used as an indicator of descending pain inhibitory function. It has been proposed as a potential biomarker for chronic pain, based on the assumption that impaired endogenous pain inhibition is characteristic of many chronic pain conditions.
📍A systematic review by Carina Fernandes et al. (2019) evaluated the concurrent validity of CPM as a biomarker of chronic pain across 48 studies with approximately 3000 participants were examined.
CONCURRENT VALIDITY:
📝The authors specifically examined whether CPM responses consistently differ between individuals with chronic pain and healthy controls, and whether CPM correlates with clinical pain outcomes such as pain intensity, area and duration, as well as pain-related disability.
FINDINGS:
📉Most correlations were non significant, with only a minority showing that poorer CPM was associated with worse clinical symptoms.
⚠️CPM has potential utility, but is not a robust standalone biomarker for chronic pain, it may be more useful as part of a multidimensional assessment, rather than in isolation.
❌Its clinical application is limited by lack of standardisation and inconsistent validity
SUMMARY:
📖While individuals with chronic pain often demonstrate reduced conditioned pain modulation, the evidence is inconsistent and weakly associated with clinical outcomes, limiting its validity as a reliable standalone biomarker of chronic pain.
MW
Reference:
Fernandes C, Pidal-Miranda M, Samartin-Veiga N, Carrillo-de-la-Peña MT. Conditioned pain modulation as a biomarker of chronic pain: a systematic review of its concurrent validity. Pain. 2019;160(12):2679–2690.

Conditioned pain modulation (CPM):Part 5: psychological factorsBACKGROUND:🔎Psychological factors such as anxiety, depres...
31/03/2026

Conditioned pain modulation (CPM):
Part 5: psychological factors
BACKGROUND:
🔎Psychological factors such as anxiety, depression, and pain catastrophizing are frequently proposed to influence pain perception, but their relationship with CPM remains unclear.
📍A meta-analysis by Hadas Nahman-Averbuch et al. (2016) synthesised the evidence from 23 experimental studies (n=1300) examining associations between psychological variables and CPM responses. The authors’ aim was to determine whether psychological factors meaningfully influence endogenous pain inhibition.
FINDINGS:
⚠️Psychological factors including pain-catastrophizing, depression and anxiety all showed weak and inconsistent associations with CPM.
SUMMARY:
❌CPM should be interpreted as part of a multifactorial pain framework, driven predominantly by neurophysiological mechanisms, rather than a purely psychological marker or state.
MW
Reference:
Nahman-Averbuch H, Nir RR, Sprecher E, Yarnitsky D. Psychological factors and conditioned pain modulation: a meta-analysis. Clin J Pain. 2016;32(6):541–554.

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The Story

‘Evidence-based practice’ is a cornerstone of good quality physiotherapy practice.

Whilst completing my post-graduate training in musculoskeletal physiotherapy, I had developed a hunger for keeping up to date with good quality contemporary research.

This page is aimed at providing high quality research reviews and summaries on contemporary topics within the field of musculoskeletal physiotherapy.

Posts within this page are structured to provide ‘easy-to-understand’ information for health professionals and health consumers, and will also endeavour to provide the relevant reference(s) for each discussion.